Quantification of modified nucleotides and nucleosides by isotope dilution mass spectrometry.

Epigenetic modifications are closely related to certain disorders of the organism, including the development of tumors. One of the main epigenetic modifications is the methylation of DNA cytosines, 5-methyl-2'-deoxycycytidine. Furthermore, 5-mdC can be oxidized to form three new modifications, 5-(hydroxymethyl)-2'-deoxycytidine, 5-formyl-2'-deoxycytidine, and 5-carboxy-2'-deoxycytidine. The coupling of liquid chromatography with tandem mass spectrometry has been widely used for the total determination of methylated DNA cytosines in samples of biological and clinical interest. These methods are based on the measurement of the free compounds (e.g., urine) or after complete hydrolysis of the DNA (e.g., tissues) followed by a preconcentration, derivatization, and/or clean-up step. This review highlights the main advances in the quantification of modified nucleotides and nucleosides by isotope dilution using isotopically labeled analogs combined with liquid or gas chromatography coupled to mass spectrometry reported in the last 20 years. The different possible sources of labeled compounds are indicated. Special emphasis has been placed on the different types of chromatography commonly used (reverse phase and hydrophilic interaction liquid chromatography) and the derivatization methods developed to enhance chromatographic resolution and ionization efficiency. We have also revised the application of bidimensional chromatography and indicated significant biological and clinical applications of these determinations.

Androgen-Dependent Prostate Cancer Cells Reprogram Their Metabolic Signature upon GLUT1 Upregulation by Manganese Superoxide Dismutase.

Prostate cancer is the second leading cause of cancer in men across the globe. The prostate gland accounts for some unique glycolytic metabolic characteristics, which causes the metabolic features of prostate tumor initiation and progression to remain poorly characterized. The mitochondrial superoxide dismutase (SOD2) is one of the major redox metabolism regulators. This study points out SOD2 as one major regulator for both redox and glycolytic metabolism in prostate cancer. SOD2 overexpression increases glucose transporter GLUT-1 and glucose uptake. This is not an insulin-mediated effect and seems to be sex-dependent, being present in male mice only. This event concurs with a series of substantial metabolic rearrangements at cytoplasmic and mitochondrial level. A concomitant decrease in glycolytic and pentose phosphate activity, and an increase in electron transfer in the mitochondrial electronic chain, were observed. The Krebs Cycle is altered to produce amino-acid intermediates by decreasing succinate dehydrogenase. This in turn generates a 13-fold increase in the oncometabolite succinate. The protein energy sensor AMPK is decreased at basal and phosphorylated levels in response to glucose deprivation. Finally, preliminary results in prostate cancer patients indicate that glandular areas presenting high levels of SOD2 show a very strong correlation with GLUT-1 protein levels (R2 = 0.287 p-value < 0.0001), indicating that in patients there may exist an analogous phenomenon to those observed in cell culture and mice.

Design and Synchronization Procedures of a D&F Co-Operative 5G Network Based on SDR Hardware Interface: Performance Analysis.

Software defined radio (SDR) is a commonly used platform for its ease of operation and cost-effectiveness for the development and testing of real wireless communication systems. By supporting high transmission rates and enabling fast and cost-effective deployments, mainly in millimeter-wave (mmWave), the co-operative 5G network has been standardized by 3GPP Release 16. In this paper, a decode-and-forward (D&F) co-operative hardware network is proposed as one of the key technologies for future 5G/6G wireless networks. The proposed system consists of an emulated base station processing unit (gnodeB), a D&F protocol and the user equipment (UE). In particular, the design of the D&F relay node is based on an MIMO layer 2 relay technology. A testbed based on an SDR platform and MatlabTM software, in which the physical broadcast channel (PBCH) transmission, physical downlink control channel (PDCCH), physical downlink shared channel (PDSCH), and downlink shared channel (DL-SCH) for transport channel coding, according to the 3GPP standardized 5G downlink signal, has been designed. The key performance indicators (KPIs), namely EVM, BER, and throughput, were measured for 5G signals with 64-QAM and 256-QAM modulation schemes. The obtained results show that the D&F co-operative 5G network achieves substantially improved KPIs in the communication between the gnodeB and the UE in an outdoor-to-indoor scenario. Furthermore, it has been demonstrated that the D&F protocol presents a good performance and behavior being compared to one commercial equipment.

A Two-Hop mmWave MIMO NR-Relay Nodes to Enhance the Average System Throughput and BER in Outdoor-to-Indoor Environments.

Millimeter-Wave (mmWave) bands are receiving enormous attention in 5G mobile communications, due to the capability to provide a multi-gigabit transmission rate. In this paper, a two-hop architecture for 5G communications with the capacity to support high end-to-end performance due to the use of Relay Nodes (RNs) in mmWave-bands is presented. One of the novelties of the paper is the implementation of Amplify-and-Forward (A&F) and Decode-and-Forward (D&F) RNs along with a mmWave-band transceiver chain (Tx/Rx). In addition, two approaches for channel estimation were implemented at the D&F RN for decoding the backhaul link. One of them assumes complete knowledge of the channel (PCE), and the other one performs the channel estimation through Least Square (LS) estimator. A large number of simulations, using MATLABTM and SimulinkTM software, were performed to verify the potential benefits of the proposal two-hop 5G architecture in an outdoor-to-indoor scenario. The main novelty in performing these simulations is the use of signals with 5G features, as DL-SCH transport channel coding, PDSCH generation, and SS Burst generation, which is another of the main contributions of the paper. On the other hand, mmWave transmitter and receiver chains were designed and implemented with off-the shelf components. The simulations show that the two-hop network substantially improves the Key Performance Indicators (KPIs), Bit Error Rate (BER), and Throughput, in the communications between the logical 5G Radio Node (gNodeB), and the New Radio User Equipment (NR-UE). For example, a throughput improvement of 22 Mbps is obtained when a 4 × 4 × 2 MIMO D&F with LS architecture is used versus a SISO D&F with PCE architecture for Signal-to-Noise Ratio (SNR) = 20 dB and 64-QAM signal. This improvement reaches 96 Mbps if a 256-QAM signal is considered. The improvement in BER is 11 dB and 10.5 dB, respectively, for both cases. This work also shows that the obtained results with D&F RNs are better than with A&F RNs. For example, an improvement of 17 Mbps in the use of SISO D&F with LS vs. SISO A&F, for the 64-QAM signal is obtained. Besides, this paper constitutes a first step to the implementation of a mmWave MIMO 5G cooperative network platform.

Melatonin Decreases Glucose Metabolism in Prostate Cancer Cells: A 13C Stable Isotope-Resolved Metabolomic Study.

The pineal neuroindole melatonin exerts an exceptional variety of systemic functions. Some of them are exerted through its specific membrane receptors type 1 and type 2 (MT1 and MT2) while others are mediated by receptor-independent mechanisms. A potential transport of melatonin through facilitative glucose transporters (GLUT/SLC2A) was proposed in prostate cancer cells. The prostate cells have a particular metabolism that changes during tumor progression. During the first steps of carcinogenesis, oxidative phosphorylation is reactivated while the switch to the "Warburg effect" only occurs in advanced tumors and in the metastatic stage. Here, we investigated whether melatonin might change prostate cancer cell metabolism. To do so, 13C stable isotope-resolved metabolomics in androgen sensitive LNCaP and insensitive PC-3 prostate cancer cells were employed. In addition to metabolite 13C-labeling, ATP/AMP levels, and lactate dehydrogenase or pentose phosphate pathway activity were measured. Melatonin reduces lactate labeling in androgen-sensitive cells and it also lowers 13C-labeling of tricarboxylic acid cycle metabolites and ATP production. In addition, melatonin reduces lactate 13C-labeling in androgen insensitive prostate cancer cells. Results demonstrated that melatonin limits glycolysis as well as the tricarboxylic acid cycle and pentose phosphate pathway in prostate cancer cells, suggesting that the reduction of glucose uptake is a major target of the indole in this tumor type.

Relationship between traditional games and the intensity of emotions experienced by participants.

PURPOSE: The aims of this study were to analyze the intensity of emotions (positive, negative, or ambiguous) produced when players took part in traditional games with a different social structure and to examine the explanations given by those participants for these emotional experiences. METHOD: Participants (N = 556) were recruited from 4 Spanish universities. After taking part in each of the games, they were asked to complete the Games and Emotions Questionnaire to indicate the intensity of their emotional experiences and to explain what, in their view, had led to the strongest emotion felt. RESULTS: The application of a mixed-methods approach identified statistically significant differences in relation to 3 variables. These were (a) the type of emotion, (b) motor domain, and (c) type of result (win, loss, and noncompetitive). The intensity of positive emotions was higher in cooperative games and lower in individual games. Comments referring to negative emotions were more frequent as the social structure of games became more complex (minimal presence of individual games and predominance of cooperation-opposition games). Winning was associated with the highest intensity ratings of positive and ambiguous emotions, whereas being defeated produced the highest values for negative emotions. The intensity ratings for negative emotions were lower in noncompetitive games than in games where players lost. CONCLUSION: The results confirm that traditional games can play a key role in relation to the emotional facets of physical education.

Effect of ball mass on dribble, pass, and pass reception in 9-11-year-old boys' basketball.

The objective of the study was to analyze the effect of ball mass on dribble, pass, and pass reception in real game situations in 9-11-year-old boys' basketball. Participants were 54 boys identified from six federated teams. The independent variable was ball mass, and dependent variables were number of dribbles, passes, and pass receptions. Three situations were established in which the participants played four games with each of the following: (a) regulation ball (485 g, 69-71 cm), (b) ball of smaller mass (440 g, 69-71 cm), and (c) ball of greater mass (540 g, 69-71 cm). Four observers recorded data from observing game videos using a computerized register instrument. Participants executed more dribbles, passes, and pass receptions with the 440g ball when compared to the regulation (p < .05) and 540g ball (p < .01). Reduction of ball mass seems to have enabled the children to go from paying attention to aspects related to ball handling to aspects of game interpretation.

Number of players who gain ball possession as a function of basketball mass among 9-11-year-old male players.

This study analyzed whether a ball with a higher (540-g) or lower (440-g) mass than the regulation ball (485-g) resulted in a larger number of participants gaining ball possession during games. Prior studies have indicated that ball handling is facilitated by decreasing the mass of the ball. It was assumed that a greater number of children gaining possession of the ball indicated greater ease of use and more control. Thus, the hypothesis was that the number of participants who gained ball possession would increase when using a ball of lower mass. The participants were 54 boys from six youth basketball teams. Participants played four games with each one of the three different balls and the number of possessions was calculated using videos of each game. The hypothesis was only partially supported: the number of participants who gained possession with the regular ball was similar to that with the 440-g ball and with the 540-g ball, but a greater number of participants gained possession with the 440-g ball in comparison to the 540-g ball. This result suggests balls that differ by more than 65 g may affect actual game outcomes.

Effect of first ball possession on partial and final scores in 2003, 2005, and 2007 Water Polo World Championships.

The purpose was to analyze the influence of winning the first ball possession on the partial and final score in male and female water polo. The 288 matches disputed by the teams participating in the 2003, 2005, and 2007 Water Polo World Championship were recorded. The results reflect statistically significant differences for the influence of gaining the first ball possession on the partial and final scoreboard of each period and for the influence between the total number of first possessions obtained and the final result.

Review of rule modification in sport.

The goal of this qualitative review was to analyze the state of the bibliography about rule modification in sport. In the literature reviewed, there are few studies of rule modification and related aspects. Most studies omit mentioning the purpose of the modifications, but they do refer to the goals of their analysis (improving players' performance, attracting spectators and athletes, attending to commercial pressure, adapting the sport to children's needs and interests, preventing injuries). Eighty percent of the studies did not report the outcome of the previous modifications they analyzed. More than half of the studies (60%) achieved the proposed goals. Nearly two-thirds (63.83%) analyzed the effect of rule modification on game actions occurring during the game or through a test. Most of the studies (91.5%) did not consult the participants. Three-fourths of the studies (74.46%) examined the effect of rule modification without any knowledge of a previous analysis or without any previous analysis, and 74.47% studied rule modification related to internal logic. Modifications to be introduced in a sport should be analyzed through a reflective process before their final introduction. The following points should be considered: establishing goals, respecting the basic rules without modifying them, becoming familiar with players' and coaches' opinions, determining the effect of the modification on a wide spectrum of variables, elaborating useful proposals for the organizations that are responsible for competitions, using more than one type of data, modifying the internal logic and, preferably, the functional rules, and following some basic stages to consolidate rule modification. Key pointsRule modification involves processes that seek change in the game conditions with a certain goal in mind.The rules related to internal logic model the game actions that are characteristic of a sport.Functional rules facilitate achieving the goals.There are few valid research studies on which to base the modifications.Modifications in a sport should be validated after a reflective process before they are introduced.

Using a dual-stable isotope tracer method to study the uptake, xylem transport and distribution of Fe and its chelating agent from stereoisomers of an Fe(III)-chelate used as fertilizer in Fe-deficient Strategy I plants.

A dual-stable isotope tracer experiment was carried out with Fe-deficient sugar beet plants grown hydroponically and resupplied with differentially Fe labeled racemic and meso Fe(iii)-chelates of the ethylendiamine di(o-hydroxyphenylacetic) acid (o,oEDDHA). No short-term Fe isotope exchange reactions occurred in the nutrient solution and plants did not discriminate between (54)Fe and (57)Fe. After 3-6 h, stable Fe isotopes, chelating agents and chelates were analyzed in roots, xylem sap and leaves by ICP-MS and HPLC-ESI/TOFMS. Ferric chelate reductase rates, xylem transport and total uptake were 2-fold higher with the meso isomer than with the racemic one. Both chelating agent isomers were incorporated and distributed by plants at similar rates, in amounts one order of magnitude lower than those of Fe. After 6 h of Fe resupply, most of the Fe acquired was localized in roots, whereas most of the chelating agent was in leaves. In a separate experiment, Fe-deficient sugar beet and tomato plants were treated with different concentrations of Fe(iii)-o,oEDDHA (with a meso/racemic ratio of 1). The xylem sap Fe concentration at 24 h was unaffected by the chelate concentration, with xylem Fe(iii)-o,oEDDHA accounting for 1-18% of total Fe and xylem meso/racemic ratio close to 1. Although most of the Fe coming from Fe(iii)-o,oEDDHA was taken up through a reductive dissociative mechanism, a small part of the Fe may be taken up via non-dissociative mechanisms.

Effect of the 3-point line change on the game dynamics in girls' minibasketball.

We examined the game dynamics in minibasketball when comparing two different forms of the 3-point line. During the first competition, participants used a 3-point line delimited by the free-throw lane, and 1,642 ball possessions were recorded. During the second competition, participants played with a 3-point line delimited by a rectangular area, and 1,669 ball possessions were recorded. Results from the Mann-Whitney U Test show that when playing with a 3-point line delimited by the free-throw lane, higher average values were achieved in terms of points scored, number of players taking part in the ball possessions, number of passes, and one-on-one situations.