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Physical education, along with the other fundamental motor activities in the field, is an integral part of the measures regarding harmonious physical development and maintaining an optimal state of health. The specialized literature, from the last period, is rich in studies, articles and works that analyze the content and way of organizing physical education and sports activities. It requires the finding of new methods and means by which to act in practice and the continuous improvement of the existing ones, of the so-called classic, traditional ones based on the new objectives facing this educational object. The importance of motor skills also emerges from the fact that an appreciable number of practitioners and theoreticians of the field argue that the whole set of motor actions and especially their execution method depend to a large extent on the level of development of these skills. This research aims to carry out a theoretical and practical study on the possibilities of developing the forms of force manifestation.

The discipline of physical education and sports through its means leads to the growth and development of the human body. Within the activities carried out during classes, physical education must achieve its objectives, by maintaining an optimal state of health, developing motor skills, learning motor skills and practicing physical exercises. Identifying the anthropometric profile of secondary school students could lead to the optimization of calendar planning and, why not, to the adaptation of educational programs to the discipline of physical education according to somatic development. The main goal is to determine the anthropometric profile of the 8th grade boys from the Iorgu Vârnav Liteanu Technological High School. In the constatative study, I studied specialized works on physical education, used the method of observation, the method of somatic evaluation and systematized the obtained data.

In the last decades, children and young people in most countries have seen an accelerated growth of some development indices, therefore the average values ​​of the height and weight of children today are higher than in the last century, sexual maturity being earlier. After the end of the growth process, which occurs more quickly, the adult’s dimensions are larger. Growth processes are characterized by the enlargement of organs, body segments and body weight. The development of the individual is highlighted by the differences that appear from a morphological, physiological and biochemical point of view. The research methods used in the confirmative study allowed us to study specialized works in the field of physical education, to observe the attitude of students during physical education classes, to evaluate the level of somatic development of girls in the 8th grade, to present, process and interpret the results obtained.

Physical education in general and sports games in particular offer multiple means by which the physical and mental development of students is achieved. All the means, carefully selected and optimally dosed, put into practice through participative-active methods, have an increased efficiency regarding technical training, educating the motor qualities required by the game, but also important for behavioral changes, the formation of moral qualities – will necessary for any young person to his integration into society. The method of studying the specialized literature allowed us to study specialized works in the field of physical education, the observation method made it possible to observe the attitude of the students within the experiment, the statistical method helped us process the results obtained from a mathematical-statistical point of view, and the method graphical and tabular in presenting data using tables and graphs. The objective of the test method was to ascertain and highlight the evolution of previously established groups of students. The purpose of the research is to evaluate the initial level of development and physical training of students in the 7th grade.

Physical education is an important factor in the development of the individual and in increasing the physical and mental potential of the individual. The handball sport game is a basic means of physical education through the motor actions carried out organized during the lessons. The lesson is coordinated by the teacher, who in the activities he carries out must ensure an attractive climate, optimal for movement and with maximum efficiency in the exercises he carries out. The activity climate must be one based on mutual respect, thus preventing conflicts between teacher and student. The method of studying the literature allowed us to study the specialized works of physical education, the method of observation made it possible to observe the attitude of students in the experiment, the statistical method helped us to process the results obtained from a mathematical-statistical point of view. graphs and tables in the presentation of data using tables and graphs. The test method aimed to ascertain and highlight the evolution of the groups of students previously established specifically for the game of handball. The aim of the research is to apply the means specific to the game of handball at the level of the gymnasium cycle, in the seventh grade, in order to achieve the objectives of physical education and school programs in order to increase the efficiency of the physical education and sports lesson.

Physical education is an important factor in the development of the individual and in increasing the physical and mental potential of the individual. The handball sport game is a basic means of physical education through the motor actions carried out organized during the lessons. The lesson is coordinated by the teacher, who in the activities he carries out must ensure an attractive climate, optimal for movement and with maximum efficiency in the exercises he carries out. The activity climate must be one based on mutual respect, thus preventing conflicts between teacher and student. The method of studying the literature allowed us to study the specialized works of physical education, the method of observation made it possible to observe the attitude of students in the experiment, the statistical method helped us to process the results obtained from a mathematical-statistical point of view. graphs and tables in the presentation of data using tables and graphs. The test method aimed to ascertain and highlight the evolution of the groups of students previously established specifically for the game of handball. The aim of the research is to apply the means specific to the game of handball at the level of the gymnasium cycle, in the seventh grade, in order to achieve the objectives of physical education and school programs in order to increase the efficiency of the physical education and sports lesson.

Intense electromagnetic fields (EMFs) induce DNA double stranded breaks (DSBs) in exposed lymphocytes.We study developing pre-B lymphocytes following V(D)J recombination at their Immunoglobulin light chain loci (IgL). Recombination physiologically induces DNA DSBs, and we tested if low doses of EMF irradiation affect this developmental stage. Recombining pre-B cells, were exposed for 48 h to low intensity EMFs (maximal radiative power density flux S of 9.5 µW/cm 2 and electric field intensity 3 V/m) from waves of frequencies ranging from 720 to 1224 MHz. Irradiated pre-B cells show decreased levels of recombination, reduction which is dependent upon the power dose and most remarkably upon the frequency of the applied EMF. Although 50% recombination reduction cannot be obtained even for an S of 9.5 µW/cm 2 in cells irradiated at 720 MHz, such an effect is reached in cells exposed to only 0.45 µW/cm 2 power with 950 and 1000 MHz waves. A maximal four-fold recombination reduction was measured in cells exposed to 1000 MHz waves with S from 0.2 to 4.5 µW/cm 2 displaying normal levels of γH2AX phosphorylated histone. Our findings show that developing B cells exposure to low intensity EMFs can affect the levels of production and diversity of their antibodies repertoire.

Currently, used antiretroviral HIV therapy drugs exclusively target critical groups in the enzymes essential for the viral life cycle. Increased mutagenesis of their genes changes these viral enzymes, which once mutated can evade therapeutic targeting, effects which confer drug resistance. To circumvent this, our review addresses a strategy to design and derive HIV-Integrase (HIV-IN) inhibitors which simultaneously target two IN functional domains, rendering it inactive even if the enzyme accumulates many mutations. First we review the enzymatic role of IN to insert the copied viral DNA into a chromosome of the host T lymphocyte, highlighting its main functional and structural features to be subjected to inhibitory action. From a functional and structural perspective we present all classes of HIV-IN inhibitors with their most representative candidates. For each chosen compound we also explain its mechanism of IN inhibition. We use the recently resolved cryo EM IN tetramer intasome DNA complex onto which we dock various reference IN inhibitory chemical scaffolds such as to target adjacent functional IN domains. Pairing compounds with complementary activity, which dock in the vicinity of a IN structural microdomain, we design bifunctional new drugs which may not only be more resilient to IN mutations but also may be more potent inhibitors than their original counterparts. In the end of our review we propose synthesis pathways to link such paired compounds with enhanced synergistic IN inhibitory effects., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

V(D)J recombination is initiated by RAG1 and RAG2, which together with HMGB1 bind to a recombination signal sequence (12RSS or 23RSS) to form the signal complex (SC) and then capture a complementary partner RSS, yielding the paired complex (PC). Little is known regarding the structural changes that accompany the SC to PC transition or the structural features that allow RAG to distinguish its two asymmetric substrates. To address these issues, we analyzed the structure of the 12RSS in the SC and PC using fluorescence resonance energy transfer (FRET) and molecular dynamics modeling. The resulting models indicate that the 12RSS adopts a strongly bent V-shaped structure upon RAG/HMGB1 binding and reveal structural differences, particularly near the heptamer, between the 12RSS in the SC and PC. Comparison of models of the 12RSS and 23RSS in the PC reveals broadly similar shapes but a distinct number and location of DNA bends as well as a smaller central cavity for the 12RSS. These findings provide the most detailed view yet of the 12RSS in RAG-DNA complexes and highlight structural features of the RSS that might underlie activation of RAG-mediated cleavage and substrate asymmetry important for the 12/23 rule of V(D)J recombination., (© The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.)

In all jawed vertebrates RAG (recombination activating gene) recombinase orchestrates V(D)J recombination in B and T lymphocyte precursors, assembling the V, D and J germline gene segments into continuous functional entities which encode the variable regions of their immune receptors. V(D)J recombination is the process by which most of the diversity of our specific immune receptors is acquired and is thought to have originated by domestication of a transposon in the genome of a vertebrate.  RAG acts similarly to the cut and paste transposases, by first binding two recombination signal DNA sequences (RSSs), which flank the two coding genes to be adjoined, in a process called synaptic or paired complex (PC) formation. At these RSS-coding borders, RAG first nicks one DNA strand, then creates hairpins, thus cleaving the duplex DNA at both RSSs. Although RAG reaction mechanism resembles that of insect mobile element transposases and RAG itself can inefficiently perform intramolecular and intermolecular integration into the target DNA, inside the nuclei of the developing lymphocytes transposition is extremely rare and is kept under proper surveillance. Our review may help understand how RAG synaptic complex organization prevents deleterious transposition. The phosphoryl transfer reaction mechanism of RNAseH-like fold DDE motif enzymes, including RAG, is discussed accentuating the peculiarities described for various transposases from the light of their available high resolution structures (Tn5, Mu, Mos1 and Hermes). Contrasting the structural 3D organization of DNA in these transpososomes with that of the RSSs-DNA in RAG PC allows us to propose several clues for how evolutionarily RAG may have become "specialized" in recombination versus transposition., Competing Interests: Conflict of interests: There are no conflicts of interest., (Copyright © 2014, Applied Systems.)

During V(D)J recombination, recombination activating gene proteins RAG1 and RAG2 generate DNA double strand breaks within a paired complex (PC) containing two complementary recombination signal sequences (RSSs), the 12RSS and 23RSS, which differ in the length of the spacer separating heptamer and nonamer elements. Despite the central role of the PC in V(D)J recombination, little is understood about its structure. Here, we use fluorescence resonance energy transfer to investigate the architecture of the 23RSS in the PC. Energy transfer was detected in 23RSS substrates in which the donor and acceptor fluorophores flanked the entire RSS, and was optimal under conditions that yield a cleavage-competent PC. The data are most easily explained by a dramatic bend in the 23RSS that reduces the distance between these flanking regions from >160 Å in the linear substrate to <80 Å in the PC. Analysis of multiple fluorescent substrates together with molecular dynamics modeling yielded a model in which the 23RSS adopts a U shape in the PC, with the spacer located centrally within the bend. We propose that this large bend facilitates simultaneous recognition of the heptamer and nonamer, is critical for proper positioning of the active site and contributes to the 12/23 rule.

The products of recombination-activating genes RAG1 and RAG2 mediate the assembly of antigen receptor genes during lymphocyte development in a process known as V(D)J recombination. Lack of structural information for the RAG proteins has hindered mechanistic studies of this reaction. We report here the crystal structure of an essential DNA binding domain of the RAG1 catalytic core bound to its nonamer DNA recognition motif. The RAG1 nonamer binding domain (NBD) forms a tightly interwoven dimer that binds and synapses two nonamer elements, with each NBD making contact with both DNA molecules. Biochemical and biophysical experiments confirm that the two nonamers are in close proximity in the RAG1/2-DNA synaptic complex and demonstrate the functional importance of the protein-DNA contacts revealed in the structure. These findings reveal a previously unsuspected function for the NBD in DNA synapsis and have implications for the regulation of DNA binding and cleavage by RAG1 and RAG2.

A critical step in V(D)J recombination is the synapsis of complementary (12/23) recombination signal sequences (RSSs) by the RAG1 and RAG2 proteins to generate the paired complex (PC). Using a facilitated ligation assay and substrates that vary the helical phasing of the RSSs, we provide evidence that one particular geometric configuration of the RSSs is favored in the PC. To investigate this configuration further, we used fluorescent resonance energy transfer (FRET) to detect the synapsis of fluorescently labeled RSS oligonucleotides. FRET requires an appropriate 12/23 RSS pair, a divalent metal ion, and high-mobility-group protein HMGB1 or HMGB2. Energy transfer between the RSSs was detected with all 12/23 RSS end positions of the fluorescent probes but was not detected when probes were placed on the two ends of the same RSS. Energy transfer was confirmed to originate from the PC by using an in-gel FRET assay. The results argue against a unique planar configuration of the RSSs in the PC and are most easily accommodated by models in which synapsed 12- and 23-RSSs are bent and cross one another, with implications for the organization of the RAG proteins and the DNA substrates at the time of cleavage.

V(D)J recombination requires binding and synapsis of a complementary (12/23) pair of recombination signal sequences (RSSs) by the RAG1 and RAG2 proteins, aided by a high-mobility group protein, HMG1 or HMG2. Double-strand DNA cleavage within this synaptic, or paired, complex is thought to involve DNA distortion or melting near the site of cleavage. Although V(D)J recombination normally occurs between RSSs located on the same DNA molecule (in cis), all previous studies that directly assessed RSS synapsis were performed with the two DNA substrates in trans. To overcome this limitation, we have developed a facilitated circularization assay using DNA substrates of reduced length to assess synapsis of RSSs in cis. We show that a 12/23 pair of RSSs is the preferred substrate for synapsis of cis RSSs and that the efficiency of pairing is dependent upon RAG1-RAG2 stoichiometry. Synapsis in cis occurs rapidly and is kinetically favored over synapsis of RSSs located in trans. This experimental system also allowed the generation of underwound DNA substrates containing pairs of RSSs in cis. Importantly, we found that the RAG proteins cleave such substrates substantially more efficiently than relaxed substrates and that underwinding may enhance RSS synapsis as well as RAG1/2-mediated catalysis. The energy stored in such underwound substrates may be used in the generation of DNA distortion and/or protein conformational changes needed for synapsis and cleavage. We propose that this unwinding is uniquely sensed during synapsis of an appropriate 12/23 pair of RSSs.

Typical of many transcriptional regulatory proteins, the lambdoid bacteriophage repressors bind cooperatively to multiple sites on DNA. This cooperative binding is essential for establishment and maintenance of phage lysogeny. In the phage, two repressor homodimers, one bound at each of the adjacent operator sites, interact to form the tetramer that is necessary for the cooperative binding of the repressor. Bacteriophage 434 repressor does not form tetramers in the absence of DNA, and the mechanism by which the tetramer assembles on the two adjacent sites is unknown. Hence DNA binding may stimulate the repressor to form tetramers and formation of a repressor oligomer (> or = 3 monomers) on a single DNA sites may precede multisite binding. Consistent with these ideas, a complex containing three repressor molecules readily assembles on a single operator (O(R)1) site. Mutations that inhibit cooperative tetramer binding to the adjacent O(R)1 and O(R)2 sites also block formation of this complex. Together with other evidence, these findings show that the complex that forms on a single site assembles using the same interface as does the tetramer assembled on adjacent operator sites. Adding additional O(R)1 DNA dissociates the oligomeric repressor-DNA complexes into dimeric repressor-O(R)1 complexes. In contrast, adding O(R)2 to these complexes results in the formation of a repressor oligomer containing an O(R)2 and an O(R)1 site. The observation that a repressor oligomer bound to two O(R)1 sites is less stable than the one formed between repressor dimers bound to O(R)1 and O(R)2 implies that DNA allosterically influences the structure of the 434 repressor. Together these findings suggest that an O(R)1-bound repressor may cooperatively help repressor bind to O(R)2 by recruiting an additional repressor molecule from solution that subsequently occupies O(R)2.

The RAG1 and RAG2 proteins together constitute the nuclease that initiates the assembly of immunoglobulin and T cell receptor genes in a reaction known as V(D)J recombination. RAG1 plays a central role in recognition of the recombination signal sequence (RSS) by the RAG1/2 complex. To investigate the parameters governing the RAG1-RSS interaction, the murine core RAG1 protein (amino acids 377-1008) fused to a short Strep tag has been purified to homogeneity from bacteria. The Strep-RAG1 (StrRAG1) protein exists as a dimer at a wide range of protein concentrations (25-500 nM) in the absence of DNA and binds with reasonably high affinity and specificity (apparent K(D) = 41 nM) to the RSS. Both electrophoretic mobility shift assays and polarization anisotropy experiments indicate that only a single StrRAG1-DNA species exists in solution. Anisotropy decay measured by frequency domain spectroscopy suggests that the complex contains a dimer of StrRAG1 bound to a single DNA molecule. Using measurements of protein intrinsic fluorescence and circular dichroism, we demonstrate that StrRAG1 undergoes a major conformational change upon binding the RSS. Steady-state fluorescence and acrylamide quenching studies reveal that this conformational change is associated with a repositioning of intrinsic protein fluorophores from a hydrophobic to a solvent-exposed environment. RSS-induced conformational changes of StrRAG1 may influence the interaction of RAG1 with RAG2 and synaptic complex formation.

Surgical interventions for morbid obesity are common practice in many countries, especially when other treatment options have failed or when rapid weight loss is desired. The association between weight and blood pressure is well established, especially the paradigm of obesity-related hypertension. We describe a 45-year-old obese woman with a medical history of hypertension and type 2 diabetes mellitus who lost 57 kg within a few months after a weight reduction surgery. She suffered from severe orthostatic hypotension, which probably resulted from sympathetic nervous system dysfunction. Our patient's clinical status improved with pharmacological interventions, but her symptoms resolved completely after she gained weight following a surgical reversal of the gastric partitioning owing to a local complication. Autonomic nervous system activity does change with the changes in body weight, but after evaluation of this patient, we believe that rapid weight loss may impair sympathetic function and blood pressure control. Although losing weight is a known treatment option for hypertension, exaggerated reversal of obesity-related hypertension might result in orthostatic hypotension.

Abstract The binding of proteins to specific DNA sequences plays a central role in the regulation of gene expression. Crucial to understanding how these proteins exert their effects is insight into the structure and flexibility of the protein-DNA complex. Over the past several years much has been learned about how the intimate contacts made between proteins and DNA enable proteins to recognize and bind with high specificity only to their cognate DNA binding sites. Studies conducted in our laboratory have shown that sequence-specific binding of DNA by proteins not only involves the close approach of amino acids and base pairs in the binding site, but also that base pairs not in contact with the protein affect binding and specificity through sequence-specific effects on DNA structure. The direct reading of the DNA sequence by proteins occurs by chemical complementarity between the interacting groups. Proper alignment of the interacting surfaces of functional groups on the protein and DNA molecules is crucial to the formation of stable and specific protein-DNA complexes. In many cases, the appropriate juxtaposition of the chemically complementary groups requires mutual adjustments in the structure of protein and DNA. Failure to do so can result in loss of affinity, loss of specificity or both. Together, the dimer interface and noncontacted bases within or adjacent to the binding site direct the structural complementarity between the functional groups on the protein and DNA.

Although bacteriophage 434 repressor binds to its specific DNA sites only as a dimer, formation of the dimers in solution occurs at concentrations three orders of magnitude higher than those needed to bind the 434 operator DNA. Our results suggest that both specific and non-specific DNA induce conformational changes in repressor that lead to formation of repressor dimers. The repressor conformational changes induced by DNA occur at concentrations much lower than those needed for binding of repressor, suggesting that the alternative conformations of repressor persist even if the protein is not in direct contact with DNA. Hence, DNA acts in a "catalytic" fashion to induce a steady-state amount of an alternative repressor conformation that has an enhanced affinity for its specific binding site. These findings suggest that the repressor conformer induced by non-specific DNA is the form of the repressor that is optimized for searching for DNA binding sites along non-specific DNA. Upon finding a binding site, the repressor protein undergoes an additional conformational change that allows it to "lock-on" to its specific site., (Copyright 1999 Academic Press.)

This new replicative model here explained is the result of the fact that, even if replication and transcription are distinct events during the cell evolution, they are functionally correlated, being responsible both for the main features of the cell, and for hormones affinity, too. This model of replication suggests the spreading of replication, in both directions symmetrically from the origin site of each replicon, as well as a simultaneous replication of both DNA strands, despite the fact that one of them was until now called "lagging" strand. These two events are explained by initiation of each DNA catena with distinct RNA polymerase forms depending on the presence or absence of the sigma 70 recognition factor (or its beta gamma analogous eukaryotic factor). The arguments sustaining these events were gathered from many already known genetic studies, some of them being here supposed to new interpretations (for instance, the phi x 174, M13 phages replication models). The disposition of both DNA strands during replication allows the intervening of both RNA polymerase types only in RNA primer synthesis. However, other physical restrictive interactions suggested theoretically prevent the going on of RNA polymerases activity like they do during transcription. This is the main reason that determines the exposure of DNA conformational changes occurring in the replication. These explanations may bring a possible new light about the "mystery" of the phenomenon producing the "replicative eye" inside the double helical structure of DNA.

From the beginning I want to explain some interesting notions about cytodifferentiation, these being seen, in my view, like an Instructive Informatory Theory. Then, I tried to present the sustaining arguments for an extracellular differentiation. These arguments reveal that final decision in differentiation process are the receptor molecules. Therefore, I present some actual questions arisen about the correlations between receptors and secondary messengers. The hormones action models are the single way to clear up the vagueness about the nucleus-receptor connection.