The relationship between isometric force-time curve characteristics and club head speed in recreational golfers

ABSTRACT: Leary, BK, Statler, J, Hopkins, B, Fitzwater, R, Kesling, T, Lyon, J, Phillips, B, Bryner, RW, Cormie, P, and Haff, GG. The relationship between isometric force-time curve characteristics and club head speed in recreational golfers. J Strength Cond Res 26(10): 2685-2697, 2012-The primary purpose of the present investigation was to examine the relationships between club head speed, isometric midthigh pull performance, and vertical jump performance in a cohort of recreational golfers. Twelve recreational golfers (age, 20.4 ± 1.0 years; weight, 77.0 ± 9.8 kg; height, 177.8 ± 6.3 cm; body fat, 17.1 ± 7.6%; handicap, 14.5 ± 7.3; experience, 8.9 ± 3.6 years) completed 3 testing sessions: (a) familiarization session and body composition measurements; (b) measurement of force-time curves in the isometric midthigh pull, countermovement, and static vertical jump (SJ); and (c) measurement of club head speed. During sessions 1 and 2, subjects performed 5 countermovement jumps, 5 SJ, and 2 isometric midthigh pulls. Isometric peak force was measured at 30, 50, 90, 100, 200, and 250 milliseconds. Rate of force development was measured among 0-30, 0-50, 0-90, 0-100, 0-200, and 0-250 milliseconds. Peak rate of force development was determined as the highest value in a 10-millisecond sampling windows. During session 3, subjects performed 10 maximal golf swings with a driver to measure club head speed; peak and average club head speed were analyzed across the 10 swings. Golf handicap was moderately correlated with average (r = -0.52, p = 0.04) and maximal club head speed (r = -0.45, p = 0.07). Force at 150 milliseconds during the isomeric midthigh pull test was moderately correlated with average (r = 0.46, p = 0.07) and maximal club head speed (r = 0.47, p = 0.06). Moderate correlations were also found between the rate of force development from 0 to 150 milliseconds and average (r = 0.38, p = 0.11) and maximal club head speed (r = 0.36, p = 0.12). The present findings suggest that the ability to exhibit high ground reaction forces in time frames <200 milliseconds are related to high club head speeds.     

The fine specificity of mannose-binding and galactose-binding lectins revealed using outlier motif analysis of glycan array data

Glycan-binding proteins are commonly used as analytical reagents to detect the levels of specific glycan structures in biological samples. A detailed knowledge of the specificities of glycan-binding proteins is required for properly interpreting their binding data. A powerful technology for characterizing glycan-binding specificity is the glycan array. However, the interpretation of glycan-array data can be difficult due to the complex fine specificities of certain glycan-binding proteins. We developed a systematic approach, called outlier-motif analysis, for extracting fine-specificity information from glycan-array data, and we applied the method to the study of four commonly used lectins: two mannose binders (concanavalin A and Lens culinaris) and two galactose binders (Bauhinia purpurea and peanut agglutinin). The study confirmed the known, primary specificity of each lectin and also revealed new insights into their binding preferences. Lens culinaris's main specificity may be non-terminal, α-linked mannose with a single linkage at its 2' carbon, which is more restricted than previous definitions. We found broader specificity for bauhinea purpurea (BPL) than previously reported, showing that BPL can bind terminal N-acetylgalactosamine (GalNAc) and penultimate β-linked galactose under certain limitations. Peanut agglutinin may bind terminal Galβ1,3Gal, a glycolipid motif, in addition to terminal Galβ1,3GalNAc, a common O-linked glycoprotein motif. These results could be used to more accurately interpret data obtained using these well-studied lectins. Furthermore, this study demonstrates a systematic and general approach for extracting fine-specificity information from glycan-array data.     

Co-delivery of Adipose-Derived Stem Cells and Growth Factor-Loaded Microspheres in RGD-Grafted N-Methacrylate Glycol Chitosan Gels for Focal Chondral Repair

The coencapsulation of growth factor-loaded microspheres with adipose-derived stem cells (ASCs) within a hydrogel matrix was studied as a potential means to enhance ASC chondrogenesis in the development of a cell-based therapeutic strategy for the regeneration of partial thickness chondral defects. A photopolymerizable N-methacrylate glycol chitosan (MGC) was employed to form an in situ gel used to encapsulate microspheres loaded with bone morphogenetic protein 6 (BMP-6) and transforming growth factor-β3 (TGF-β3) with human ASCs. ASC viability and retention were enhanced when the Young's modulus of the MGC ranged between 225 and 380 kPa. Grafting an RGD-containing peptide onto the MGC backbone (RGD-MGC) improved ASC viability within the gels, remaining at greater than 90% over 14 days in culture. The effects of BMP-6 and TGF-β3 released from the polymer microspheres on ASC chondrogenesis were assessed, and the level of differentiation was compared to ASCs in control gels containing nongrowth factor-loaded microspheres cultured with and without the growth factors supplied in the medium. There was enhanced expression of chondrogenic markers at earlier time points when the ASCs were induced with the sustained and local release of BMP-6 and TGF-β3 from the microspheres. More specifically, the normalized glycosaminoglycan and collagen type II protein expression levels were significantly higher than in the controls. In addition, the ratio of collagen type II to type I was significantly higher in the microsphere delivery group and increased over time. End-point RT-PCR analysis supported that there was a more rapid induction and enhancement of ASC chondrogenesis in the controlled release group. Interestingly, in all of the assays, there was evidence of chondrogenic differentiation when the ASCs were cultured in the gels in the absence of growth factor stimulation. Overall, the co-delivery of growth-factor-loaded microspheres and ASCs in RGD-modified MGC gels successfully induced ASC chondrogenesis and is a promising strategy for cartilage repair.     

Quantile-based permutation thresholds for quantitative trait Loci hotspots

Quantitative trait loci (QTL) hotspots (genomic locations affecting many traits) are a common feature in genetical genomics studies and are biologically interesting since they may harbor critical regulators. Therefore, statistical procedures to assess the significance of hotspots are of key importance. One approach, randomly allocating observed QTL across the genomic locations separately by trait, implicitly assumes all traits are uncorrelated. Recently, an empirical test for QTL hotspots was proposed on the basis of the number of traits that exceed a predetermined LOD value, such as the standard permutation LOD threshold. The permutation null distribution of the maximum number of traits across all genomic locations preserves the correlation structure among the phenotypes, avoiding the detection of spurious hotspots due to nongenetic correlation induced by uncontrolled environmental factors and unmeasured variables. However, by considering only the number of traits above a threshold, without accounting for the magnitude of the LOD scores, relevant information is lost. In particular, biologically interesting hotspots composed of a moderate to small number of traits with strong LOD scores may be neglected as nonsignificant. In this article we propose a quantile-based permutation approach that simultaneously accounts for the number and the LOD scores of traits within the hotspots. By considering a sliding scale of mapping thresholds, our method can assess the statistical significance of both small and large hotspots. Although the proposed approach can be applied to any type of heritable high-volume "omic" data set, we restrict our attention to expression (e)QTL analysis. We assess and compare the performances of these three methods in simulations and we illustrate how our approach can effectively assess the significance of moderate and small hotspots with strong LOD scores in a yeast expression data set.     

人源抗滋养层细胞表面抗原?鄄2基因工程抗体Fab的制备及特性分析

应用噬菌体抗体库技术制备全人源抗滋养层细胞表面抗原-2(Trop-2)特异性Fab抗体片段．抗体库经细胞筛选和固相抗原筛选,获得特异性的阳性克隆．阳性载体经核酸序列分析后,构建工程菌,经IPTG诱导表达,SDS-PAGE和Western blot分析,呈现28 ku和32 ku大小的两条蛋白质条带．Fab分子经流式细胞术、细胞免疫荧光检测,结果表明,Fab能够与BxPc3细胞膜蛋白特异性结合,而与NIH3T3细胞不结合．免疫共沉淀与质谱分析结果表明,该Fab分子能够与Trop-2蛋白特异性结合．免疫组化显示,该抗体可结合胰腺癌细胞膜蛋白,在细胞培养液中加入Fab,能够抑制BxPc3细胞的生长．以上研究结果提示,该抗体有望成为胰腺癌临床影像诊断或治疗的候选分子．     

Ubiquitin-conjugating Enzyme Cdc34 and Ubiquitin Ligase Skp1-Cullin-F-box Ligase (SCF) Interact through Multiple Conformations

In the ubiquitin-proteasome system, protein substrates are degraded via covalent modification by a polyubiquitin chain. The polyubiquitin chain must be assembled rapidly in cells, because a chain of at least four ubiquitins is required to signal for degradation, and chain-editing enzymes in the cell may cleave premature polyubiquitin chains before achieving this critical length. The ubiquitin-conjugating enzyme Cdc34 and ubiquitin ligase SCF are capable of building polyubiquitin chains onto protein substrates both rapidly and processively; this may be explained at least in part by the atypically fast rate of Cdc34 and SCF association. This rapid association has been attributed to electrostatic interactions between the acidic C-terminal tail of Cdc34 and a feature on SCF called the basic canyon. However, the structural aspects of the Cdc34-SCF interaction and how they permit rapid complex formation remain elusive. Here, we use protein cross-linking to demonstrate that the Cdc34-SCF interaction occurs in multiple conformations, where several residues from the Cdc34 acidic tail are capable of contacting a broad region of the SCF basic canyon. Similar patterns of cross-linking are also observed between Cdc34 and the Cul1 paralog Cul2, implicating the same mechanism for the Cdc34-SCF interaction in other members of the cullin-RING ubiquitin ligases. We discuss how these results can explain the rapid association of Cdc34 and SCF.     

Xanthine Oxidoreductase Function Contributes to Normal Wound Healing

Chronic, nonhealing wounds result in patient morbidity and disability. Reactive oxygen species (ROS) and nitric oxide (NO) are both required for normal wound repair, and derangements of these result in impaired healing. Xanthine oxidoreductase (XOR) has the unique capacity to produce both ROS and NO. We hypothesize that XOR contributes to normal wound healing. Cutaneous wounds were created in C57Bl6 mice. XOR was inhibited with dietary tungsten or allopurinol. Topical hydrogen peroxide (H₂O₂, 0.15%) or allopurinol (30 μg) was applied to wounds every other day. Wounds were monitored until closure or collected at d 5 to assess XOR expression and activity, cell proliferation and histology. The effects of XOR, nitrite, H₂O₂ and allopurinol on keratinocyte cell (KC) and endothelial cell (EC) behavior were assessed. We identified XOR expression and activity in the skin and wound edges as well as granulation tissue. Cultured human KCs also expressed XOR. Tungsten significantly inhibited XOR activity and impaired healing with reduced ROS production with reduced angiogenesis and KC proliferation. The expression and activity of other tungsten-sensitive enzymes were minimal in the wound tissues. Oral allopurinol did not reduce XOR activity or alter wound healing but topical allopurinol significantly reduced XOR activity and delayed healing. Topical H₂O₂ restored wound healing in tungsten-fed mice. In vitro, nitrite and H₂O₂ both stimulated KC and EC proliferation and EC migration. These studies demonstrate for the first time that XOR is abundant in wounds and participates in normal wound healing through effects on ROS production.