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Muscle tendon unit fibre mechanics of hamstring and adductor strain injuries are not well studied, with factors such as fatigue promoted as risk factors in the absence of mechanistic evidence. In this study, musculoskeletal modelling was used to estimate fibre mechanics of four hamstring (biceps femoris long head, biceps femoris short head, semimembranosus and semitendinosus) and four adductor (adductor brevis, adductor longus, adductor magnus and gracilis) muscles during an anticipated cut task. The cut task was performed by 10 healthy elite male U20 basketball players both before and immediately after they played in one (of four) competitive basketball game. Biceps femoris long head produced significantly lower (p = 0.032) submaximal force post-game in the latter part of swing (30.7% to 35.0% of stride), though its peak force occurred later (37%) and remained unchanged. Semimembranosus produced significantly lower (p = 0.006) force post-game (32.9% to 44.9% of stride), which encompassed the instance of peak force (39%). Neither fibre velocity nor fibre length of the investigated muscles were significantly affected by game-play. These finding suggest that if fatigue is a factor in hamstring and adductor muscle strain injuries and is brought about by game-play, it is unlikely through the fibre mechanisms investigated in this study.

Objectives: To identify if basketball players aged <20 years (U20) self-report hip and/or groin pain and if they perceive this as a problem. To determine potential differences in self-reported playing (training and match play) loads and Copenhagen Hip and Groin Outcome Score (HAGOS) between those with and without hip/groin pain., Design: Cross-sectional., Methods: Fifty-one pre-elite (state/national representative level) male U20 basketball players (Australian n=38; Italian n=13) self-reported current/historical hip/groin 'discomfort/pain' and 'problems', and playing loads. A two-factor regression model was fitted including main effects for hip/groin pain and Cohort and their interaction, with outcome variables playing loads and HAGOS subscale scores and dependent variable hip/groin pain., Results: Twenty-one players (41%) self-reported hip/groin 'discomfort/pain', of which nine perceived no 'problems'. Two of these nine players reported training/playing time loss due to pain. Those self-reporting hip/groin discomfort/pain scored lower than those without in HAGOS subscales Symptoms (mean difference in score 8.94; 95%CI -25.24, -5.97), Pain (5.00; -16.42, -2.81), Function in daily living (0.00; -26.72 to -5.59), Function in sport and recreation (6.25; -21.24, -5.33), and hip and/or groin Quality of Life (5.00; -28.63, -8.10), indicating worse hip/groin problems. Participation subscale scores were different only for Italian players (36.25; -51.25, -20.00), with players self-reporting hip/groin discomfort/pain scoring lower., Conclusion: Most players who perceive both hip/groin 'discomfort/pain' and 'problems' also report training/playing time loss, suggesting players' perceptions of problematic symptoms and time-loss are associated. Adolescent basketball players perceive hip/groin pain to negatively impact their daily lives and sporting function., (Copyright © 2021 Sports Medicine Australia. All rights reserved.)

High stage and recurrent ovarian clear cell carcinoma (OCC) are associated with poor prognosis and resistance to chemotherapy. A distinguishing histological feature of OCC is abundant cytoplasmic stores of glucose, in the form of glycogen, that can be mobilized for cellular metabolism. Here, we report the effect on preclinical models of OCC of disrupting glycogen utilization using the glucose analogue 2-deoxy-D-glucose (2DG). At concentrations significantly lower than previously reported for other cancers, 2DG markedly improves the efficacy in vitro of carboplatin chemotherapy against chemo-sensitive TOV21G and chemo-resistant OVTOKO OCC cell lines, and this is accompanied by the depletion of glycogen. Of note, 2DG doses-of more than 10-fold lower than previously reported for other cancers-significantly improve the efficacy of carboplatin against cell line and patient-derived xenograft models in mice that mimic the chemo-responsiveness of OCC. These findings are encouraging, in that 2DG doses, which are substantially lower than previously reported to cause adverse events in cancer patients, can safely and significantly improve the efficacy of carboplatin against OCC. Our results thus justify clinical trials to evaluate whether low dose 2DG improves the efficacy of carboplatin in OCC patients.

Elevated CUB-domain containing protein 1 (CDCP1) is predictive of colorectal cancer (CRC) recurrence and poor patient survival. While CDCP1 expression identifies stem cell populations that mediate lung metastasis, mechanisms underlying the role of this cell surface receptor in CRC have not been defined. We sought to identify CDCP1 regulated processes in CRC using stem cell populations, enriched from primary cells and cell lines, in extensive in vitro and in vivo assays. These experiments, demonstrating that CDCP1 is functionally important in CRC tumor initiation, growth and metastasis, identified CDCP1 as a positive regulator of Wnt signaling. Detailed cell fractionation, immunoprecipitation, microscopy, and immunohistochemical analyses demonstrated that CDCP1 promotes translocation of the key regulators of Wnt signaling, β-catenin, and E-cadherin, to the nucleus. Of functional importance, disruption of CDCP1 reduces nuclear localized, chromatin-associated β-catenin and nuclear localized E-cadherin, increases sequestration of these proteins in cell membranes, disrupts regulation of CRC promoting genes, and reduces CRC tumor burden. Thus, disruption of CDCP1 perturbs pro-cancerous Wnt signaling including nuclear localization of β-catenin and E-cadherin.

Chromatography of glutaraldehyde-fixed skim-milk on controlled-pore glass (CPG-10, 300 nm) gave three micellar fractions whose averaged diameters, measured by electron microscopy, decreased progressively with increasing elution volume. Casein micelles with diameters up to 680 nm were detected. The casein composition of the same fractions from unfixed skim-milk was determined. As the fraction elution volume increased, kappa-casein varied from 7.7 to 11.4% of total casein, giving alpha s/kappa ratios of 6.1, 4.7 and 3.3. A plot of kappa-casein content versus micelle surface-to-volume ratio for skim-milk and the column fractions approximated to a straight line. Re-calculation of the published results from two other studies also gave linear relationships between kappa-casein content and surface area for artificial micelles. The three regression lines thus obtained had small intercepts. It was concluded that the data indicated the same fundamental structure for casein micelles, with a predominant surface location for kappa-casein, whether the micelles are natural or artificial and whether they are aggregated by Ca2+ alone or by Ca2+ together with calcium phosphate-citrate complex.

Skim-milk was fractionated by permeation chromatography on CPG-10 (300 nm) at 20 degrees C with synthetic milk serum. The elution profile, which was highly reproducible, showed 3 partly resolved peaks. On treatment with 0.1% glutaraldehyde before chromatography, a similar profile was obtained indicating no appreciable micellar dissociation during chromatography of the milk. The casein composition of the eluent fractions, determined by quantitative chromatography on hydroxyapatite, showed that 12.1% of total casein was associated with the low molecular weight peak. The micelle content of beta- and kappa-casein increased with increasing elution volume, and the alphas/kappa ratio showed a progressive diminution from 4.3 to 2.3. Large differences were found in the colloidal phosphate contents and the weight average diameters of the micelle fractions which clearly show that CPG-10 fractionates on the basis of molecular size.

Casein micelles of bovine skimmed milk were fractionated by permeation chromatography on porous glass (CPG-10, 50 nm followed by CPG-10, 300 nm) at 30 degrees C. Micelles were pooled in eight eluant fractions and their size distribution was determined by electron microscopy. The composition of casein in the eight fractions was determined by quantitative hydroxyapatite chromatography. Micelle size decreased progressively with increasing elution volume, and volume-to-surface average diameter ranged from 154 nm in fraction 1 to 62 nm in fraction 8. Concurrently there was a decrease in relative proportions of alpha s- and beta-caseins and a large enrichment of kappa-casein, which changed from 4.1% total casein in fraction 1 to 12.1% total casein in fraction 8. At least half the decrease in alpha s-casein proportions was attributed to the alpha s1-casein component, but the data also suggested a decline in proportions of alpha s2-casein in the smallest micelle fractions. A plot of kappa-casein fractional content versus micelle surface-to-volume ratio gave a straight line (correlation coefficient from linear regression 0.98) from which an average kappa-casein surface coverage of 1.5 m2/mg or 47.3 nm2/molecule was obtained. If a constant surface coverage for kappa-casein is assumed, the parameters of the linear equation predict that micelle voluminosity is inversely related to micelle diameter, being approximately 30% larger in fraction 8 compared to fraction 1.

Bovine milk systems were analysed for adenosine 5'-triphosphate (ATP) using the luciferase-ATP reaction in a liquid scintillation counter. Approximately 0.2 mumol ATP/l milk serum were evident both in whole milks and the corresponding skim-milks. ATP was not detectable in skim-milk ultrafiltrates. These findings indicated that ATP was present in a non-dialysable portion of skim-milk. Centrifugation of whole milks from individual cows at 5500 g for 15 min at 10 degrees C yielded skim-milks essentially devoid of somatic cells and bacteria. However, the ATP in the skim-milks decreased by less than 20% compared with the whole milks indicating that the calcium phosphate-citrate (CPC)--caseinate micelles were the source of the ATP. ATP was not detectable in colloidal phosphate-free milk, from which CPC had been removed, confirming that the ATP was sequestered in the constituent CPC. Likewise, the occurrence of significant amounts of Mg, another potent stabilizer of amorphous calcium phosphate (ACP) in other biological systems, was confirmed in the colloidal phosphate of milk. From 0.13 to 0.31 mumole ATP/1 (mean 0.23) was found in the 9 milk samples studied. The discovery of small but appreciable levels of ATP in the CPC of milk provides further evidence for the analogy previously shown to exist between the CPC complex of milk and the ACP which accumulates in mitochondria. The latter has been postulated to provide an essential precursor for crystalline bone salts to form in ordered calcification processes. The implications of these findings in the biosynthesis of milk are briefly discussed.