An early start at a professional soccer academy is no prerequisite for world cup soccer participation.

Introduction: 829 players from 32 nations on five continents participated in the 2022 men's World Cup tournament in Qatar. Not much is known about the youth careers of World Cup players from all over the world, especially about the age at which they began playing youth soccer in a professional academy. This study aimed to provide insights in the age national team players participating in World Cup Qatar 2022 started playing for a professional soccer academy and whether their starting age relates to continent and their current playing position (i.e., goalkeepers, defenders, midfielders, and forwards). Method: Systematic online desk research was conducted to determine the age at which World Cup players started playing for professional youth soccer organizations. The median and interquartile ranges were expressed for the starting age in professional youth soccer organizations and the current age at the World Cup. The variables were compared with playing position, the continent of the player's World Cup nation, and the continent on which the player was raised. Results: The results reveal that World Cup Qatar 2022 players started playing for professional soccer academies at a median age of 13.2 years (range: 4.2-22.6). In Europe, players started playing for professional youth soccer organizations earlier than players on other continents [χ2 (4) = 142.0, p < 0.001]. We also found a younger starting age in forwards than goalkeepers (p < 0.05). Discussion: In most established soccer nations in Europe and South-America, World Cup players started playing for professional soccer academies before the age of 12. However, a significant number of players started later, especially players on other continents, which reveals the different pathways youth players can follow to the elites.

The origin of suspended particulate matter in the Great Barrier Reef.

River run-off has long been regarded as the largest source of organic-rich suspended particulate matter (SPM) in the Great Barrier Reef (GBR), contributing to high turbidity, pollutant exposure and increasing vulnerability of coral reef to climate change. However, the terrestrial versus marine origin of the SPM in the GBR is uncertain. Here we provide multiple lines of evidence (13C NMR, isotopic and genetic fingerprints) to unravel that a considerable proportion of the terrestrially-derived SPM is degraded in the riverine and estuarine mixing zones before it is transported further offshore. The fingerprints of SPM in the marine environment were completely different from those of terrestrial origin but more consistent with that formed by marine phytoplankton. This result indicates that the SPM in the GBR may not have terrestrial origin but produced locally in the marine environment, which has significant implications on developing better-targeted management practices for improving water quality in the GBR.

Differences in Acceleration and High-Intensity Activities Between Small-Sided Games and Peak Periods of Official Matches in Elite Soccer Players.

ABSTRACT: Dalen, T, Sandmæl, S, Stevens, TGA, Hjelde, GH, Kjøsnes, TN, and Wisløff, U. Differences in acceleration and high-intensity activities between small-sided games and peak periods of official matches in elite soccer players. J Strength Cond Res 35(7): 2018-2024, 2021-The purpose of this study was to compare whether the physical performance of players during 4 vs. 4 + goalkeeper (4 vs. 4) and 6 vs. 6 + goalkeeper (6 vs. 6) small-sided games (SSGs) is equivalent to those experienced during the most intense 5-minute period of soccer match play. Twenty-six male soccer players from an elite Norwegian league team took part. Players were monitored during 18 matches, 56 SSGs: twenty-eight 4 vs. 4 and twenty-eight 6 vs. 6 games. The ZXY Sport Tracking System was used to measure for each player the total distance covered, high-intensity running distance, sprint distance, number of accelerations, and player load (all expressed per minute). To compare the physical performance variables on players during the SSGs formats and match play, a 1-way analysis of variance with repeated measures was used. Players performed the same number of accelerations and player load in 4 vs. 4 (1.7 and 248, respectively) as in peak match (1.6 and 227, respectively), whereas in 6 vs. 6, there were 63% fewer accelerations and 15% lower player load (1.2 and 198, respectively), than in peak match. High-intensity running and sprint distance were significantly lower than mean match values in both 4 vs. 4 (4.1 and 0.2 m vs. 8.2 and 1.7 m) and 6 vs. 6 games (2.7 and 0.21 m vs. 8.2 and 1.7 m) (p < 0.05). In conclusion, only 4 vs. 4 SSGs are highly valuable, and in that, they elicit player load and accelerations to a level that is (at least) equivalent with peak periods of official match play.

Mutations in the V-ATPase Assembly Factor VMA21 Cause a Congenital Disorder of Glycosylation With Autophagic Liver Disease.

BACKGROUND AND AIMS: Vacuolar H+-ATP complex (V-ATPase) is a multisubunit protein complex required for acidification of intracellular compartments. At least five different factors are known to be essential for its assembly in the endoplasmic reticulum (ER). Genetic defects in four of these V-ATPase assembly factors show overlapping clinical features, including steatotic liver disease and mild hypercholesterolemia. An exception is the assembly factor vacuolar ATPase assembly integral membrane protein (VMA21), whose X-linked mutations lead to autophagic myopathy. APPROACH AND RESULTS: Here, we report pathogenic variants in VMA21 in male patients with abnormal protein glycosylation that result in mild cholestasis, chronic elevation of aminotransferases, elevation of (low-density lipoprotein) cholesterol and steatosis in hepatocytes. We also show that the VMA21 variants lead to V-ATPase misassembly and dysfunction. As a consequence, lysosomal acidification and degradation of phagocytosed materials are impaired, causing lipid droplet (LD) accumulation in autolysosomes. Moreover, VMA21 deficiency triggers ER stress and sequestration of unesterified cholesterol in lysosomes, thereby activating the sterol response element-binding protein-mediated cholesterol synthesis pathways. CONCLUSIONS: Together, our data suggest that impaired lipophagy, ER stress, and increased cholesterol synthesis lead to LD accumulation and hepatic steatosis. V-ATPase assembly defects are thus a form of hereditary liver disease with implications for the pathogenesis of nonalcoholic fatty liver disease.

ATP6AP2 functions as a V-ATPase assembly factor in the endoplasmic reticulum.

ATP6AP2 (also known as the [pro]renin receptor) is a type I transmembrane protein that can be cleaved into two fragments in the Golgi apparatus. While in Drosophila ATP6AP2 functions in the planar cell polarity (PCP) pathway, recent human genetic studies have suggested that ATP6AP2 could participate in the assembly of the V-ATPase in the endoplasmic reticulum (ER). Using a yeast model, we show here that the V-ATPase assembly factor Voa1 can functionally be replaced by Drosophila ATP6AP2. This rescue is even more efficient when coexpressing its binding partner ATP6AP1, indicating that these two proteins together fulfill Voa1 functions in higher organisms. Structure-function analyses in both yeast and Drosophila show that proteolytic cleavage is dispensable, while C-terminus-dependent ER retrieval is required for ATP6AP2 function. Accordingly, we demonstrate that both overexpression and lack of ATP6AP2 causes ER stress in Drosophila wing cells and that the induction of ER stress is sufficient to cause PCP phenotypes. In summary, our results suggest that full-length ATP6AP2 contributes to the assembly of the V-ATPase proton pore and that impairment of this function affects ER homeostasis and PCP signaling.

NK cell function is markedly impaired in patients with chronic lymphocytic leukaemia but is preserved in patients with small lymphocytic lymphoma.

Chronic lymphocytic leukemia (B-CLL) and small lymphocytic lymphoma (SLL) are part of the same disease classification but are defined by differential distribution of tumor cells. B-CLL is characterized by significant immune suppression and dysregulation but this is not typical of patients with SLL. Natural killer cells (NK) are important mediators of immune function but have been poorly studied in patients with B-CLL/SLL. Here we report for the first time the NK cell phenotype and function in patients with B-CLL and SLL alongside their transcriptional profile. We show for the first time impaired B-CLL NK cell function in a xenograft model with reduced activating receptor expression including NKG2D, DNAM-1 and NCRs in-vitro. Importantly, we show these functional differences are associated with transcriptional downregulation of cytotoxic pathway genes, including activating receptors, adhesion molecules, cytotoxic molecules and intracellular signalling molecules, which remain intact in patients with SLL. In conclusion, NK cell function is markedly influenced by the anatomical site of the tumor in patients with B-CLL/SLL and lymphocytosis leads to marked impairment of NK cell activity. These observations have implications for treatment protocols which seek to preserve immune function by limiting the exposure of NK cells to tumor cells within the peripheral circulation.

ATP6AP1 deficiency causes an immunodeficiency with hepatopathy, cognitive impairment and abnormal protein glycosylation.

The V-ATPase is the main regulator of intra-organellar acidification. Assembly of this complex has extensively been studied in yeast, while limited knowledge exists for man. We identified 11 male patients with hemizygous missense mutations in ATP6AP1, encoding accessory protein Ac45 of the V-ATPase. Homology detection at the level of sequence profiles indicated Ac45 as the long-sought human homologue of yeast V-ATPase assembly factor Voa1. Processed wild-type Ac45, but not its disease mutants, restored V-ATPase-dependent growth in Voa1 mutant yeast. Patients display an immunodeficiency phenotype associated with hypogammaglobulinemia, hepatopathy and a spectrum of neurocognitive abnormalities. Ac45 in human brain is present as the common, processed ∼40-kDa form, while liver shows a 62-kDa intact protein, and B-cells a 50-kDa isoform. Our work unmasks Ac45 as the functional ortholog of yeast V-ATPase assembly factor Voa1 and reveals a novel link of tissue-specific V-ATPase assembly with immunoglobulin production and cognitive function.

Validity and reliability of 6-a-side small-sided game locomotor performance in assessing physical fitness in football players.

In order to determine whether small-sided game (SSG) locomotor performance can serve as a fitness indicator, we (1) compared 6-a-side (6v6) SSG-intensity of players varying in fitness and skill, (2) examined the relationship of the 6v6-SSG and Yo-Yo IR2 and (3) assessed the reliability of the 6v6-SSG. Thirty-three professional senior, 30 professional youth, 62 amateur and 16 professional woman football players performed 4 × 7 min 6v6-SSGs recorded by a Local Position Measurement system. A substantial subgroup (N = 113) also performed the Yo-Yo IR2. Forty-seven amateur players performed two or three 6v6-SSGs. No differences in 6v6-SSG time-motion variables were found between professional senior and professional youth players. Amateurs showed lower values than professional seniors on almost all time-motion variables (ES = 0.59-1.19). Women displayed lower high-intensity time-motion variables than all other subgroups. Total distance run during 6v6-SSG was only moderately related to Yo-Yo IR2 distance (r = 0.45), but estimated metabolic power, high speed (>14.4 km · h(-1)), high acceleration (>2 m · s(-2)), high power (>20 W · kg(-1)) and very high (35 W · kg(-1)) power showed higher correlations (r = 0.59-0.70) with Yo-Yo IR2 distance. Intraclass correlation coefficient values were higher for total distance (0.84) than other time-motion variables (0.74‒0.78). Although total distance and metabolic power during 6v6-SSG showed good reproducibility (coefficient of variation (CV) < 5%), CV was higher (8-14%) for all high-intensity time-motion variables. It was therefore concluded that standardised SSG locomotor performance cannot serve used as a valid and reliable fitness indicator for individual players.

Measured and estimated energy cost of constant and shuttle running in soccer players.

PURPOSE: Players in team sports like soccer often make acceleration and deceleration movements, which are more energetically demanding than running at constant speed. The first aim of the present study was to estimate this difference in associated energy cost. To this end, we compared the actual energy cost of shuttle running to that of running at constant speed. In addition, since measuring oxygen consumption is not feasible during soccer, the study's second aim was to determine the validity of an indirect approach to estimate energy cost provided by di Prampero et al. (2005) using time-motion data obtained from a tracking system as input. METHODS: Fourteen male amateur soccer players performed aerobic constant and continuous shuttle running at six different speeds (range = 7.5-10.0 km·h⁻¹) on artificial turf. Measured energy cost was compared to the energy cost estimated with di Prampero's (2005) equation using data from a local position measurement (LPM) system as input. RESULTS: As expected, measured energy cost was significantly higher (∼30%-50%) for shuttle running than for constant running (P < 0.001), and this difference increased with speed. For constant running, estimated energy cost was significantly higher (6%-11%) than measured energy cost, whereas for shuttle running, estimated energy cost was significantly lower (-13% to -16%) than measured energy cost. CONCLUSIONS: Shuttle running raised the player's energy cost of running compared to constant running at the same average speed. Although actual energy cost of constant running was significantly overestimated by di Prampero's approach using LPM data as input, actual energy cost of shuttle running was significantly underestimated.

Homotypic vacuole fusion in yeast requires organelle acidification and not the V-ATPase membrane domain.

Studies of homotypic vacuole-vacuole fusion in the yeast Saccharomyces cerevisiae have been instrumental in determining the cellular machinery required for eukaryotic membrane fusion and have implicated the vacuolar H(+)-ATPase (V-ATPase). The V-ATPase is a multisubunit, rotary proton pump whose precise role in homotypic fusion is controversial. Models formulated from in vitro studies suggest that it is the proteolipid proton-translocating pore of the V-ATPase that functions in fusion, with further studies in worms, flies, zebrafish, and mice appearing to support this model. We present two in vivo assays and use a mutant V-ATPase subunit to establish that it is the H(+)-translocation/vacuole acidification function, rather than the physical presence of the V-ATPase, that promotes homotypic vacuole fusion in yeast. Furthermore, we show that acidification of the yeast vacuole in the absence of the V-ATPase rescues vacuole-fusion defects. Our results clarify the in vivo requirements of acidification for membrane fusion.

Design of an accuracy study for position detection in football.

Only a few studies have analysed the accuracy of position detection systems. All of them analysed distances and velocities, which are the outcome of calculations based on x,y positions. The objective of this study was to analyse the accuracy of dynamic x,y position measurement of a radar- and an image-based system in football. One and two runners performed five different runs on four different locations on a football pitch. X,y positions recorded by the radar-based and the image-based system were compared to x,y positions measured by a Laveg laser device. Accuracies were analysed by means of root mean square error (RMSE). Results showed that the radar-based system detects positions more accurately than the image-based system (P = 0.000). Mean RMSE of the radar-based system was 0.24 m, RMSE of the image-based system was 0.73 m. The image-based system was significantly influenced by the location of the run, whereas the radar-based system was not. Based on the results of this study, we conclude that the radar-based system is more valid in detecting x,y positions than the image-based system. Future studies should take advantage of the new test design which allows more precise statements on the accuracy of a position detection system.

SEMAT--the next generation of inexpensive marine environmental monitoring and measurement systems.

There is an increasing need for environmental measurement systems to further science and thereby lead to improved policies for sustainable management. Marine environments are particularly hostile and extremely difficult for deploying sensitive measurement systems. As a consequence the need for data is greatest in marine environments, particularly in the developing economies/regions. Expense is typically the most significant limiting factor in the number of measurement systems that can be deployed, although technical complexity and the consequent high level of technical skill required for deployment and servicing runs a close second. This paper describes the Smart Environmental Monitoring and Analysis Technologies (SEMAT) project and the present development of the SEMAT technology. SEMAT is a "smart" wireless sensor network that uses a commodity-based approach for selecting technologies most appropriate to the scientifically driven marine research and monitoring domain/field. This approach allows for significantly cheaper environmental observation systems that cover a larger geographical area and can therefore collect more representative data. We describe SEMAT's goals, which include: (1) The ability to adapt and evolve; (2) Underwater wireless communications; (3) Short-range wireless power transmission; (4) Plug and play components; (5) Minimal deployment expertise; (6) Near real-time analysis tools; and (7) Intelligent sensors. This paper illustrates how the capacity of the system has been improved over three iterations towards realising these goals. The result is an inexpensive and flexible system that is ideal for short-term deployments in shallow coastal and other aquatic environments.

Sorting of the yeast vacuolar-type, proton-translocating ATPase enzyme complex (V-ATPase): identification of a necessary and sufficient Golgi/endosomal retention signal in Stv1p.

Subunit a of the yeast vacuolar-type, proton-translocating ATPase enzyme complex (V-ATPase) is responsible for both proton translocation and subcellular localization of this highly conserved molecular machine. Inclusion of the Vph1p isoform causes the V-ATPase complex to traffic to the vacuolar membrane, whereas incorporation of Stv1p causes continued cycling between the trans-Golgi and endosome. We previously demonstrated that this targeting information is contained within the cytosolic, N-terminal portion of V-ATPase subunit a (Stv1p). To identify residues responsible for sorting of the Golgi isoform of the V-ATPase, a random mutagenesis was performed on the N terminus of Stv1p. Subsequent characterization of mutant alleles led to the identification of a short peptide sequence, W(83)KY, that is necessary for proper Stv1p localization. Based on three-dimensional homology modeling to the Meiothermus ruber subunit I, we propose a structural model of the intact Stv1p-containing V-ATPase demonstrating the accessibility of the W(83)KY sequence to retrograde sorting machinery. Finally, we characterized the sorting signal within the context of a reconstructed Stv1p ancestor (Anc.Stv1). This evolutionary intermediate includes an endogenous W(83)KY sorting motif and is sufficient to compete with sorting of the native yeast Stv1p V-ATPase isoform. These data define a novel sorting signal that is both necessary and sufficient for trafficking of the V-ATPase within the Golgi/endosomal network.

Evolution of increased complexity in a molecular machine.

Many cellular processes are carried out by molecular 'machines'-assemblies of multiple differentiated proteins that physically interact to execute biological functions. Despite much speculation, strong evidence of the mechanisms by which these assemblies evolved is lacking. Here we use ancestral gene resurrection and manipulative genetic experiments to determine how the complexity of an essential molecular machine--the hexameric transmembrane ring of the eukaryotic V-ATPase proton pump--increased hundreds of millions of years ago. We show that the ring of Fungi, which is composed of three paralogous proteins, evolved from a more ancient two-paralogue complex because of a gene duplication that was followed by loss in each daughter copy of specific interfaces by which it interacts with other ring proteins. These losses were complementary, so both copies became obligate components with restricted spatial roles in the complex. Reintroducing a single historical mutation from each paralogue lineage into the resurrected ancestral proteins is sufficient to recapitulate their asymmetric degeneration and trigger the requirement for the more elaborate three-component ring. Our experiments show that increased complexity in an essential molecular machine evolved because of simple, high-probability evolutionary processes, without the apparent evolution of novel functions. They point to a plausible mechanism for the evolution of complexity in other multi-paralogue protein complexes.

The reconstructed ancestral subunit a functions as both V-ATPase isoforms Vph1p and Stv1p in Saccharomyces cerevisiae.

The vacuolar-type, proton-translocating ATPase (V-ATPase) is a multisubunit enzyme responsible for organelle acidification in eukaryotic cells. Many organisms have evolved V-ATPase subunit isoforms that allow for increased specialization of this critical enzyme. Differential targeting of the V-ATPase to specific subcellular organelles occurs in eukaryotes from humans to budding yeast. In Saccharomyces cerevisiae, the two subunit a isoforms are the only difference between the two V-ATPase populations. Incorporation of Vph1p or Stv1p into the V-ATPase dictates the localization of the V-ATPase to the vacuole or late Golgi/endosome, respectively. A duplication event within fungi gave rise to two subunit a genes. We used ancestral gene reconstruction to generate the most recent common ancestor of Vph1p and Stv1p (Anc.a) and tested its function in yeast. Anc.a localized to both the Golgi/endosomal network and vacuolar membrane and acidified these compartments as part of a hybrid V-ATPase complex. Trafficking of Anc.a did not require retrograde transport from the late endosome to the Golgi that has evolved for retrieval of the Stv1p isoform. Rather, Anc.a localized to both structures through slowed anterograde transport en route to the vacuole. Our results suggest an evolutionary model that describes the differential localization of the two yeast V-ATPase isoforms.