Variations of training load, monotony, and strain and dose-response relationships with maximal aerobic speed, maximal oxygen uptake, and isokinetic strength in professional soccer players

This study aimed to identify variations in weekly training load, training monotony, and training strain across a 10-week period (during both, pre- and in-season phases); and to analyze the dose-response relationships between training markers and maximal aerobic speed (MAS), maximal oxygen uptake, and isokinetic strength. Twenty-seven professional soccer players (24.9±3.5 years old) were monitored across the 10-week period using global positioning system units. Players were also tested for maximal aerobic speed, maximal oxygen uptake, and isokinetic strength before and after 10 weeks of training. Large positive correlations were found between sum of training load and extension peak torque in the right lower limb (r = 0.57, 90%CI[0.15;0.82]) and the ratio agonist/antagonist in the right lower limb (r = 0.51, [0.06;0.78]). It was observed that loading measures fluctuated across the period of the study and that the load was meaningfully associated with changes in the fitness status of players. However, those magnitudes of correlations were small-to-large, suggesting that variations in fitness level cannot be exclusively explained by the accumulated load and loading profile

Phenoloxidase activity acts as a mosquito innate immune response against infection with semliki forest virus

Several components of the mosquito immune system including the RNA interference (RNAi), JAK/STAT, Toll and IMD pathways have previously been implicated in controlling arbovirus infections. In contrast, the role of the phenoloxidase (PO) cascade in mosquito antiviral immunity is unknown. Here we show that conditioned medium from the Aedes albopictus-derived U4.4 cell line contains a functional PO cascade, which is activated by the bacterium Escherichia coli and the arbovirus Semliki Forest virus (SFV) (Togaviridae; Alphavirus). Production of recombinant SFV expressing the PO cascade inhibitor Egf1.0 blocked PO activity in U4.4 cell- conditioned medium, which resulted in enhanced spread of SFV. Infection of adult female Aedes aegypti by feeding mosquitoes a bloodmeal containing Egf1.0-expressing SFV increased virus replication and mosquito mortality. Collectively, these results suggest the PO cascade of mosquitoes plays an important role in immune defence against arboviruses

Experience with onabotulinumtoxinA (BOTOX) in chronic refractory migraine: focus on severe attacks

The objective of this study is to analyse our experience in the treatment of refractory chronic migraine (CM) with onabotulinumtoxinA (BTA) and specifically in its effects over disabling attacks. Patients with CM and inadequate response or intolerance to oral preventatives were treated with pericranial injections of 100 U of TBA every 3 months. The dose was increased up to 200 U in case of no response. The patients kept a headache diary. In addition, we specifically asked on the effect of BTA on the frequency of disabling attacks, consumption of triptans and visits to Emergency for the treatment of severe attacks. This series comprises a total of 35 patients (3 males), aged 24–68 years. All except three met IHS criteria for analgesic overuse. The number of sessions with BTA ranged from 2 to 15 (median 4) and nine (26%) responded (reduction of >50% in headache days). However, the frequency of severe attacks was reduced to an average of 46%. Oral triptan consumption (29 patients) was reduced by 50% (from an average of 22 to 11 tablets/month). Those six patients who used subcutaneous sumatriptan reduced its consumption to a mean of 69% (from 4.5 to 1.5 injections per month). Emergency visits went from an average of 3 to 0.4 per trimester (−83%). Six patients complained of mild adverse events, transient local cervical pain being the most common. Although our data must be taken with caution as this is an open trial, in clinical practice treatment of refractory CM with BTA reduces the frequency of disabling attacks, the consumption of triptans and the need of visits to Emergency, which makes this treatment a profitable option both clinically and pharmacoeconomically

Large introns in relation to alternative splicing and gene evolution: a case study of Drosophila bruno-3

Background: Alternative splicing (AS) of maturing mRNA can generate structurally and functionally distinct transcripts from the same gene. Recent bioinformatic analyses of available genome databases inferred a positive correlation between intron length and AS. To study the interplay between intron length and AS empirically and in more detail, we analyzed the diversity of alternatively spliced transcripts (ASTs) in the Drosophila RNA-binding Bruno-3 (Bru-3) gene. This gene was known to encode thirteen exons separated by introns of diverse sizes, ranging from 71 to 41,973 nucleotides in D. melanogaster. Although Bru-3's structure is expected to be conducive to AS, only two ASTs of this gene were previously described. Results: Cloning of RT-PCR products of the entire ORF from four species representing three diverged Drosophila lineages provided an evolutionary perspective, high sensitivity, and long-range contiguity of splice choices currently unattainable by high-throughput methods. Consequently, we identified three new exons, a new exon fragment and thirty-three previously unknown ASTs of Bru-3. All exon-skipping events in the gene were mapped to the exons surrounded by introns of at least 800 nucleotides, whereas exons split by introns of less than 250 nucleotides were always spliced contiguously in mRNA. Cases of exon loss and creation during Bru-3 evolution in Drosophila were also localized within large introns. Notably, we identified a true de novo exon gain: exon 8 was created along the lineage of the obscura group from intronic sequence between cryptic splice sites conserved among all Drosophila species surveyed. Exon 8 was included in mature mRNA by the species representing all the major branches of the obscura group. To our knowledge, the origin of exon 8 is the first documented case of exonization of intronic sequence outside vertebrates. Conclusion: We found that large introns can promote AS via exon-skipping and exon turnover during evolution likely due to frequent errors in their removal from maturing mRNA. Large introns could be a reservoir of genetic diversity, because they have a greater number of mutable sites than short introns. Taken together, gene structure can constrain and/or promote gene evolution

An E2F1-Mediated DNA Damage Response Contributes to the Replication of Human Cytomegalovirus

DNA damage resulting from intrinsic or extrinsic sources activates DNA damage responses (DDRs) centered on protein kinase signaling cascades. The usual consequences of inducing DDRs include the activation of cell cycle checkpoints together with repair of the damaged DNA or induction of apoptosis. Many DNA viruses elicit host DDRs during infection and some viruses require the DDR for efficient replication. However, the mechanism by which DDRs are activated by viral infection is poorly understood. Human cytomegalovirus (HCMV) infection induces a DDR centered on the activation of ataxia telangiectasia mutated (ATM) protein kinase. Here we show that HCMV replication is compromised in cells with inactivated or depleted ATM and that ATM is essential for the host DDR early during infection. Likewise, a downstream target of ATM phosphorylation, H2AX, also contributes to viral replication. The ATM-dependent DDR is detected as discrete, nuclear γH2AX foci early in infection and can be activated by IE proteins. By 24 hpi, γH2AX is observed primarily in HCMV DNA replication compartments. We identified a role for the E2F1 transcription factor in mediating this DDR and viral replication. E2F1, but not E2F2 or E2F3, promotes the accumulation of γH2AX during HCMV infection or IE protein expression. Moreover, E2F1 expression, but not the expression of E2F2 or E2F3, is required for efficient HCMV replication. These results reveal a novel role for E2F1 in mediating an ATM-dependent DDR that contributes to viral replication. Given that E2F activity is often deregulated by infection with DNA viruses, these observations raise the possibility that an E2F1-mediated mechanism of DDR activation may be conserved among DNA viruses

Homologous Recombination Is Stimulated by a Decrease in dUTPase in Arabidopsis

Deoxyuridine triphosphatase (dUTPase) enzyme is an essential enzyme that protects DNA against uracil incorporation. No organism can tolerate the absence of this activity. In this article, we show that dUTPase function is conserved between E. coli (Escherichia coli), yeast (Saccharomyces cerevisiae) and Arabidopsis (Arabidopsis thaliana) and that it is essential in Arabidopsis as in both micro-organisms. Using a RNA interference strategy, plant lines were generated with a diminished dUTPase activity as compared to the wild-type. These plants are sensitive to 5-fluoro-uracil. As an indication of DNA damage, inactivation of dUTPase results in the induction of AtRAD51 and AtPARP2, which are involved in DNA repair. Nevertheless, RNAi/DUT1 constructs are compatible with a rad51 mutation. Using a TUNEL assay, DNA damage was observed in the RNAi/DUT1 plants. Finally, plants carrying a homologous recombination (HR) exclusive substrate transformed with the RNAi/DUT1 construct exhibit a seven times increase in homologous recombination events. Increased HR was only detected in the plants that were the most sensitive to 5-fluoro-uracils, thus establishing a link between uracil incorporation in the genomic DNA and HR. Our results show for the first time that genetic instability provoked by the presence of uracils in the DNA is poorly tolerated and that this base misincorporation globally stimulates HR in plants

Long-term postharvest aroma evolution of tomatoes with the alcobaça (alc) mutation

The postharvest evolution of Penjar tomatoes has been studied in four accessions representative of the variability of the varietal type. The long-term shelf life of these materials, which carry the alc allele, was confirmed with 31.2-59.1% of commercial fruits after 6 months of effective conservation at room temperature and a limited loss of weight (21.1-27.9%). Aroma in Penjar tomatoes is differentiated from other tomato varieties by a characteristic 'sharp-floral' aroma descriptor. The evolution of the 'sharp-floral' aroma during postharvest showed a peak of intensity at 2 months of postharvest, though in one accession a delay of 2 months in this response was detected. Out of 25 volatiles analysed, including main and background notes, a reverse iPLS variable selection revealed that the main candidates behind this aromatic behaviour are ¿-terpineol, trans-2-hexenal, 6-methyl-5-hepten-2-one, trans-2-octenal, ¿-pinene, ß-ionone, 2 + 3-methylbutanol and phenylacetaldehyde. Between harvest and 2 months postharvest, most compounds reduced considerably their concentration, while the intensity of the 'sharp-floral' descriptor increased, which means that probably there is a rearrangement of the relative concentrations among volatiles that may lead to masking/unmasking processes. © 2011 Springer-Verlag.This work was supported by grants from the Conselleria de Agricultura, Pesca y Alimentacio de la Comunidad Valenciana, the Fundacion de la Comunidad Valenciana para la Investigacion Agroalimentaria (AGROALIMED) and from the Departament d'Agricultura, Alimentacio i Accio Rural (DAR) de la Generalitat de Catalunya.Casals Missio, J.; Cebolla Cornejo, J.; Rosello Ripolles, S.; Beltran Arandes, J.; Casanas, F.; Nuez Viñals, F. (2011). Long-term postharvest aroma evolution of tomatoes with the alcobaça (alc) mutation. European Food Research and Technology. 233(2):331-342. doi:10.1007/s00217-011-1517-6S3313422332Petro-Turza M (1987) Flavor of tomato and tomato products. Food Rev Int 2:309–351Butterry RG (1993) Quantitative and sensory aspects of flavor of tomato and other vegetables and fruits. In: Acree TE, Teranishi R (eds) Flavor science: sensible principles and techniques. American Chemical Society, WashingtonGoff SA, Klee HJ (2006) Plant volatile compounds: sensory cues for health and nutritional value? Science 311:815–819Tieman DM, Zeigler M, Schmelz EA, Taylor MG, Bliss P, Kirst M, Klee MJ (2006) Identification of loci affecting flavour volatile emissions in tomato fruits. J Exp Bot 57:887–896Zanor MI, Rambla JL, Chaïb J, Steppa A, Medina A, Granell A, Fernie AR, Causse M (2009) Metabolic characterization of loci affecting sensory attributes allows an assessment of the influence of the levels of primary metabolites and volatile organic contents. J Exp Bot 60:2139–2154Ortiz-Serrano P, Gil JV (2010) Quantitative comparison of free and bound volatiles of two commercial tomato cultivars (Solanum lycopersicum L.) during ripening. J Agric Food Chem 58:1106–1114Boukobza F, Taylor AJ (2002) Effect of postharvest treatment on flavour volatiles of tomatoes. Postharvest Biol Technol 25:321–331Vrebalov J, Ruezinsky D, Padmanabhan V, White R, Medrano D, Drake R, Schuch W, Giovannoni J (2002) A MADS-box gene necessary for fruit ripening at the tomato ripening-inhibitor (rin) locus. Science 296:343–346Giovannoni JJ, Tanksley SD, Vrebalov J, Noensie E (2004) NOR gene for use in manipulation of fruit quality and ethylene response. US Patent No 5,234,834 issued 13 July 2004McGlasson WB, Last JH, Shaw KJ, Meldrum SK (1987) Influence of the non-ripening mutants rin and nor on the aroma of tomato fruit. HortScience 22:632–634Baldwin EA, Scott JW, Shewmaker CK, Schuch W (2000) Flavor trivia and tomato aroma: biochemistry and possible mechanisms for control of important aroma components. HortScience 35:1013–1022Kovács K, Rupert CF, Tikunov Y, Graham N, Bradley G, Seymour GB, Bovy AG, Grierson D (2009) Effect of pleiotropic ripening mutations on flavour volatile biosynthesis. Phytochemistry 70:1003–1008Gao HY, Zhu BZ, Zhu HL, Zhang YL, Xie YH, Li YC, Luo YB (2007) Effect of suppression of ethylene biosynthesis on flavour products in tomato fruits. Russ J Plant Physiol 54:80–88Lewinsohn E, Sitrit Y, Bar E, Azulay Y, Meir A, Zamir D, Tadmor Y (2005) Carotenoid pigmentation affects the volatile composition of tomato and watermelon fruits, as revealed by comparative genetic analyses. J Agric Food Chem 53:3142–3148Kopeliovitch E, Mizrahi Y, Rabinowitch D, Kedar N (1980) Physiology of the mutant alcobaca. Physiol Plant 48:307–311Casals J, Pacual L, Cañizares J, Cebolla-Cornejo J, Casañas F, Nuez F (2011) Genetic basis of long shelf life and variability into Penjar tomato. Genet Resour Crop Evol. doi: 10.1007/s10722-011-9677-6Kuzyomenskii AV (2007) Effect of cumulative polymery of tomato keeping life genes. Cytol Genet 41:268–275Paran I, van der Knaap E (2007) Genetic and molecular regulation of fruit and plant domestication traits in tomato and pepper. J Exp Bot 58:3841–3852Moretti CL, Baldwin EA, Sargent SA, Huber DJ (2002) Internal bruising alters aroma volatile profiles in tomato fruit tisúes. HortScience 37:378–382Buttery RG, Teranishi R, Ling LC (1987) Fresh tomato aroma volatiles: a qualitative study. J Agric Food Chem 35:540–544Romero del Castillo R, Valero J, Casañas F, Costell E (2008) Training validation and maintenance of a panel to evaluate the texture of dry beans (Phaseolus vulgaris L.). J Sens Stud 23:303–319Beltran J, Serrano E, López FJ, Peruga A, Valcárcel M, Roselló S (2006) Comparison of two quantitative GC-MS methods for analysis of tomato aroma based on purge-and-trap and on solid-phase microextraction. Anal Bioanal Chem 385:1255–1264Martens H, Naes T (1989) Multivariate Calibration. Wiley, New YorkWise BM, Gallagher NB, Bro R, Shaver JM, Windig W, Koch RS (2006) Chemometrics tutorial for PLS_Toolbox and Solo. Eigenvector Research, WenatcheeHongsoongnern P, Chambers E (2008) A lexicon for texture and flavor characteristics of fresh and processed tomatoes. J Sens Stud 23:583–599Norgaard L, Saudland A, Wagner J, Nielsen JP, Munck L, Engelsen SB (2000) Interval partial least-squares regression (iPLS): A comparative chemometric study with an example from near-infrared spectroscopy. Appl Spectrosc 54:413–419Javanmardi J, Kubota C (2006) Variation of lycopene, antioxidant activity, total soluble solids and weight loss of tomato during postharvest storage. Postharvest Biol Technol 41:151–155Kader AA (1986) Effects of postharvest handling procedures on tomato quality. Acta Hort 190:209–222Maul F, Sargent SA, Sims CA, Baldwin EA, Balaban MO, Huber DJ (2000) Tomato flavor and aroma quality as affected by storage temperature. J Food Sci 65:1228–1237Krumbein A, Auerswald H (1998) Characterization of aroma volatiles in tomatoes by sensory analyses. Nahrung 6:S395–S399Tandon KS, Baldwin EA, Shewfelt RL (2000) Aroma perception of individual volatile compounds in fresh tomatoes (Lycopersicon esculentum Mill.) as affected by the medium of evaluation. Postharvest Biol Technol 20:261–268Cebolla-Cornejo J, Roselló S, Valcárcel M, Serrano E, Beltran J, Nuez F (2011) Evaluation of genotype and environment effects on taste and aroma flavour components of Spanish fresh tomato varieties. J Agric Food Chem 59:2440–2450Carbonell-Barrachina AA, Agustí A, Ruiz JJ (2006) Analysis of flavor volatile compounds by dynamic headspace in traditional and hybrid cultivars of Spanish tomatoes. Eur Food Res Technol 222:536–542Alonso A, Vázquez-Araújo L, García-Martínez S, Ruiz JJ, Carbonell Barrachina AA (2009) Volatile compounds of traditional and virus-resistant breeding lines of Muchamiel tomatoes. Eur Food Res Technol 230:315–323Liggett E, Drake MA, Delwiche JF (2008) Impact of flavor attributes on consumer liking of Swiss cheese. J Dairy Sci 91:466–476Ortiz-Serrano P, Gil JV (2007) Quantitation of free and glycosidically bound volatiles in and effect of glycosidase addition on three tomato varieties (Solanum lycopersicum L.). J Agric Food Chem 55:9170–9176Xu Y, Barringer S (2010) Comparison of tomatillo and tomato volatile compounds in the headspace by selected ion flow tube mass spectrometry (SIFT-MS). J Food Sci 75:C268–C273Berna AZ, Lammertyn J, Saevels S, Di Natale C, Nicolai BM (2004) Electronic nose systems to study shelf life and cultivar effect on tomato aroma profile. Sens Actuators B Chem 97:324–333Baldwin EA, Scott JW, Einstein MA, Malundo TMM, Carr BT, Shewfelt RL, Tandon KS (1998) Relationship between sensory and instrumental analysis for tomato flavor. J Am Soc Hortic Sci 12:906–915Krumbein A, Peters P, Brückner B (2004) Flavour compounds and a quantitative descriptive analysis of tomatoes (Lycopersicon esculentum Mill.) of different cultivars in short-term storage. Postharvest Biol Technol 32:15–2

The presentation, clinical features, complications, and treatment of congenital dacryocystocele

Purpose To determine the incidence and presenting features of congenital dacryocystocele in the United Kingdom. To report on those cases complicated by dacryocystitis, respiratory compromise, and the treatment undertaken. Methods A prospective observational study of cases of congenital dacryocystocele presenting in the United Kingdom between September 2014 and October 2015. Infants <3 months of age presenting with a cystic swelling in the medial canthal area were included. Cases were identified via the British Ophthalmology Surveillance Unit (BOSU) reporting system. Results A total of 49 cases were reported during the study period. This gives an incidence of 1 in 18 597 live births. There was a 71% response rate to the questionnaire. The average age at presentation was 16.94 days. Dacryocystoceles were unilateral in 91% of cases. Dacryocystitis was a complicating factor in 49% of patients and 17% had respiratory distress. Uncomplicated dacryocystocele responded well to conservative measures in 86%. Surgical intervention was required in 23% of patients. Those cases complicated by dacryocystitis (29%) and nasal obstruction (17%) were more likely to require surgical intervention compared to those with dacryocystocele alone (14%). Digital massage appears to reduce the likelihood of requiring surgical intervention. The mean time to resolution was 19 days. Conclusions Congenital dacryocystocele is a rare presentation in the United Kingdom. Dacryocystitis and respiratory compromise commonly complicate a dacryocystocele. The use of digital massage as an early intervention is advocated and conservative measures may be sufficient in cases of uncomplicated dacryocystocele

Baseline Religion Involvement Predicts Subsequent Salivary Cortisol Levels Among Male But not Female Black Youth

Background: Compared to Whites, Blacks are exposed to higher levels of chronic stress in the United States. As a result, major Black-White differences exist in the baseline and response of cortisol. Yet, the potential association between baseline religiosity and subsequent cortisol levels of Blacks are not known. Objectives: In the current study we aimed to determine the association between baseline religious behaviors and daytime salivary cortisol level among male and female Black youth. Materials and Methods: With a longitudinal design, data came from wave 1 (1994) and wave 6 (2000) of a cohort from an urban area in the Midwest of the United States. The study followed 227 Black adolescents (109 males and 118 females) for six years. Socio-demographics and religious behaviors (frequency of participation in religious activities) were measured at baseline. Base morning cortisol level at wave 6 was the outcome. We fitted a linear regression model to test the association between baseline religiosity at wave 1 and cortisol level at wave 6, while baseline age, socio-economics, and psychological symptoms were controlled. Results: In the pooled sample, frequency of participation in religious activities at baseline was negatively associated with mean cortisol level at follow up (r = -0.29, P > 0.01) among all, males (r = -0.38, P > 0.01), but not females (r = -.20, P > 0.05). Frequency of participation in religious activities remained a significant predictor of subsequent cortisol level (b = -0.283, 95% CI = -.107 - -0.022) while the effect of age, socioeconomics, and psychological symptoms were controlled. We could only find such an association among male Black youth (b = -0.368, 95% CI = -0.148 - -0.024) but not female Black youth (b = -0.229, 95% CI = -.113 - 0.011). Conclusions: Religiosity has been used as a coping mechanism among Blacks. Religiosity may also be related to stress regulation among Black youth. Future studies need to test complex associations between race, sex, religiosity, chronic stress, coping, and function of hypothalamo-pituitary-adrenal (HPA). It is not known whether male Black youth who are and those who are not religious differently cope with stress associated with daily discrimination and living in disadvantaged neighborhoods