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[PMID]: 29524844
[Au] Autor:Cheng Z; Shen X; Jiang X; Shan H; Cimini M; Fang P; Ji Y; Park JY; Drosatos K; Yang X; Kevil CG; Kishore R; Wang H
[Ad] Address:Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, 3500 Broad Street, Philadelphia, PA 19140, USA. Electronic address: zjcheng@temple.edu.
[Ti] Title:Hyperhomocysteinemia potentiates diabetes-impaired EDHF-induced vascular relaxation: Role of insufficient hydrogen sulfide.
[So] Source:Redox Biol;16:215-225, 2018 Feb 14.
[Is] ISSN:2213-2317
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Insufficient hydrogen sulfide (H S) has been implicated in Type 2 diabetic mellitus (T2DM) and hyperhomocysteinemia (HHcy)-related cardiovascular complications. We investigated the role of H S in T2DM and HHcy-induced endothelial dysfunction in small mesenteric artery (SMA) of db/db mice fed a high methionine (HM) diet. HM diet (8 weeks) induced HHcy in both T2DM db/db mice and non-diabetic db/+ mice (total plasma Hcy: 48.4 and 31.3 µM, respectively), and aggravated the impaired endothelium-derived hyperpolarization factor (EDHF)-induced endothelium-dependent relaxation to acetylcholine (ACh), determined by the presence of eNOS inhibitor N(ω)-nitro-L-arginine methyl ester (L-NAME) and prostacyclin (PGI ) inhibitor indomethacin (INDO), in SMA from db/db mice but not that from db/+ mice. A non-selective Ca -active potassium channel (K ) opener NS309 rescued T2DM/HHcy-impaired EDHF-mediated vascular relaxation to ACh. EDHF-induced relaxation to ACh was inhibited by a non-selective K blocker TEA and intermediate-conductance K blocker (IK ) Tram-34, but not by small-conductance K (SK ) blocker Apamin. HHcy potentiated the reduction of free sulfide, H S and cystathionine γ-lyase protein, which converts L-cysteine to H S, in SMA of db/db mice. Importantly, a stable H S donor DATS diminished the enhanced O production in SMAs and lung endothelial cells of T2DM/HHcy mice. Antioxidant PEG-SOD and DATS improved T2DM/HHcy impaired relaxation to ACh. Moreover, HHcy increased hyperglycemia-induced IK tyrosine nitration in human micro-vascular endothelial cells. EDHF-induced vascular relaxation to L-cysteine was not altered, whereas such relaxation to NaHS was potentiated by HHcy in SMA of db/db mice which was abolished by ATP-sensitive potassium channel blocker Glycolamide but not by K blockers. CONCLUSIONS: Intermediate HHcy potentiated H S reduction via CSE-downregulation in microvasculature of T2DM mice. H S is justified as an EDHF. Insufficient H S impaired EDHF-induced vascular relaxation via oxidative stress and IK inactivation in T2DM/HHcy mice. H S therapy may be beneficial for prevention and treatment of micro-vascular complications in patients with T2DM and HHcy.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  2 / 138254 MEDLINE  
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[PMID]: 29524756
[Au] Autor:Swanberg KM; Prinsen H; Coman D; de Graaf RA; Juchem C
[Ad] Address:Department of Biomedical Engineering, Columbia University Fu Foundation School of Engineering and Applied Science, 1210 Amsterdam Ave., New York, NY 10027, United States; Department of Radiology and Biomedical Imaging, Yale University School of Medicine, 330 Cedar Street, New Haven, CT 06520, United
[Ti] Title:Quantification of glutathione transverse relaxation time T using echo time extension with variable refocusing selectivity and symmetry in the human brain at 7 Tesla.
[So] Source:J Magn Reson;290:1-11, 2018 Mar 01.
[Is] ISSN:1096-0856
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Glutathione (GSH) is an endogenous antioxidant implicated in numerous biological processes, including those associated with multiple sclerosis, aging, and cancer. Spectral editing techniques have greatly facilitated the acquisition of glutathione signal in living humans via proton magnetic resonance spectroscopy, but signal quantification at 7 Tesla is still hampered by uncertainty about the glutathione transverse decay rate T relative to those of commonly employed quantitative references like N-acetyl aspartate (NAA), total creatine, or water. While the T of uncoupled singlets can be derived in a straightforward manner from exponential signal decay as a function of echo time, similar estimation of signal decay in GSH is complicated by a spin system that involves both weak and strong J-couplings as well as resonances that overlap those of several other metabolites and macromolecules. Here, we extend a previously published method for quantifying the T of GABA, a weakly coupled system, to quantify T of the strongly coupled spin system glutathione in the human brain at 7 Tesla. Using full density matrix simulation of glutathione signal behavior, we selected an array of eight optimized echo times between 72 and 322 ms for glutathione signal acquisition by J-difference editing (JDE). We varied the selectivity and symmetry parameters of the inversion pulses used for echo time extension to further optimize the intensity, simplicity, and distinctiveness of glutathione signals at chosen echo times. Pairs of selective adiabatic inversion pulses replaced nonselective pulses at three extended echo times, and symmetry of the time intervals between the two extension pulses was adjusted at one extended echo time to compensate for J-modulation, thereby resulting in appreciable signal-to-noise ratio and quantifiable signal shapes at all measured points. Glutathione signal across all echo times fit smooth monoexponential curves over ten scans of occipital cortex voxels in nine subjects. The T of glutathione was calculated to be 145.0 ±â€¯20.1 ms (mean ±â€¯standard deviation); this result was robust within one standard deviation to changes in metabolite fitting baseline corrections and removal of individual data points on the signal decay curve. The measured T of NAA (222.1 ±â€¯24.7 ms) and total creatine (153.0 ±â€¯19.9 ms) were both higher than that calculated for GSH. Apparent glutathione concentration quantified relative to both reference metabolites increased by up to 32% and 6%, respectively, upon correction with calculated T values, emphasizing the importance of considering T relaxation differences in the spectroscopic measurement of these metabolites, especially at longer echo times.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  3 / 138254 MEDLINE  
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[PMID]: 29524386
[Au] Autor:Mohanty I; Parija SC; Suklabaidya S; Rattan S
[Ad] Address:Department of Medicine, Division of Gastroenterology and Hepatology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Pharmacology and Toxicology, College of Veterinary Sciences and Animal Husbandry, Orissa University of Agriculture and Technology, Bh
[Ti] Title:Acidosis potentiates endothelium-dependent vasorelaxation and gap junction communication in the superior mesenteric artery.
[So] Source:Eur J Pharmacol;, 2018 Mar 07.
[Is] ISSN:1879-0712
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Extracellular pH is an important physiological determinant of vascular tone that is normally maintained within 7.35-7.45. Any change outside this range leads to severe pathological repercussions. We investigated the unknown effects of extracellular acidosis on relaxation in the superior mesenteric artery (SMA) of goat. SMA rings were employed to maintain isometric contractions at extracellular pH (pH ) 7.4 and 6.8. We analyzed the effect of acidosis (pH 6.8) compared to physiological pH (pH 7.4) on three signaling mediators of endothelium-dependent hyperpolarization: nitric oxide (NO), prostaglandin I (PGI ), and myoendothelial gap junctions (MEGJ). NO and cyclic guanosine monophosphate (cGMP) levels were compared between normal and acidic pH. Quantitative real-time PCR (qPCR) studies determined the change in expression of vascular connexin (Cx), Cx37, Cx40, and Cx43. Under acidosis, acetyl choline-induced relaxation was augmented in an endothelium-dependent manner via eNOS-NO-cGMP signaling. Conversely, at normal pH, acetyl choline-induced vasorelaxation was mediated primarily via COX-PGI pathway. The functional activity of MEGJ was increased under acidosis as evident from increased sensitivity of connexin blockers and upregulated gene and protein expression of connexins. In conclusion, acetyl choline-induced augmented vasorelaxation under acidosis is mediated by NOS-NO-cGMP, with a partial role of MEGJ as EDH mediators in the SMA. Present data suggest a novel role of connexin as therapeutic targets to attenuate the detrimental effect of acidosis on vascular tone.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  4 / 138254 MEDLINE  
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[PMID]: 29524381
[Au] Autor:Slonimskiy YB; Maksimov EG; Lukashev EP; Moldenhauer M; Jeffries CM; Svergun DI; Friedrich T; Sluchanko NN
[Ad] Address:A.N. Bach Institute of Biochemistry, Federal Research Center of Biotechnology of the Russian Academy of Sciences, 119071 Moscow, Russian Federation; M.V. Lomonosov Moscow State University, Department of Biochemistry, Faculty of Biology, 119991 Moscow, Russian Federation.
[Ti] Title:Functional interaction of low-homology FRPs from different cyanobacteria with Synechocystis OCP.
[So] Source:Biochim Biophys Acta;, 2018 Mar 07.
[Is] ISSN:0006-3002
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:Photosynthesis requires a balance between efficient light harvesting and protection against photodamage. The cyanobacterial photoprotection system uniquely relies on the functioning of the photoactive orange carotenoid protein (OCP) that under intense illumination provides fluorescence quenching of the light-harvesting antenna complexes, phycobilisomes. The recently identified fluorescence recovery protein (FRP) binds to the photoactivated OCP and accelerates its relaxation into the basal form, completing the regulatory circle. The molecular mechanism of FRP functioning is largely controversial. Moreover, since the available knowledge has mainly been gained from studying Synechocystis proteins, the cross-species conservation of the FRP mechanism remains unexplored. Besides phylogenetic analysis, we performed a detailed structural-functional analysis of two selected low-homology FRPs by comparing them with Synechocystis FRP (SynFRP). While adopting similar dimeric conformations in solution and preserving binding preferences of SynFRP towards various OCP variants, the low-homology FRPs demonstrated distinct binding stoichiometries and differentially accentuated features of this functional interaction. By providing clues to understand the FRP mechanism universally, our results also establish foundations for upcoming structural investigations necessary to elucidate the FRP-dependent regulatory mechanism.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  5 / 138254 MEDLINE  
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[PMID]: 29515115
[Au] Autor:Broome MA; Gorman SK; House MG; Hile SJ; Keizer JG; Keith D; Hill CD; Watson TF; Baker WJ; Hollenberg LCL; Simmons MY
[Ad] Address:Centre of Excellence for Quantum Computation and Communication Technology, School of Physics, University of New South Wales, Sydney, NSW, 2052, Australia.
[Ti] Title:Two-electron spin correlations in precision placed donors in silicon.
[So] Source:Nat Commun;9(1):980, 2018 Mar 07.
[Is] ISSN:2041-1723
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Substitutional donor atoms in silicon are promising qubits for quantum computation with extremely long relaxation and dephasing times demonstrated. One of the critical challenges of scaling these systems is determining inter-donor distances to achieve controllable wavefunction overlap while at the same time performing high fidelity spin readout on each qubit. Here we achieve such a device by means of scanning tunnelling microscopy lithography. We measure anti-correlated spin states between two donor-based spin qubits in silicon separated by 16 ± 1 nm. By utilising an asymmetric system with two phosphorus donors at one qubit site and one on the other (2P-1P), we demonstrate that the exchange interaction can be turned on and off via electrical control of two in-plane phosphorus doped detuning gates. We determine the tunnel coupling between the 2P-1P system to be 200 MHz and provide a roadmap for the observation of two-electron coherent exchange oscillations.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180311
[Lr] Last revision date:180311
[St] Status:In-Data-Review
[do] DOI:10.1038/s41467-018-02982-x

  6 / 138254 MEDLINE  
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[PMID]: 29432808
[Au] Autor:Grønlund D; Poulsen JL; Krogh K; Brock C; Liao D; Gregersen H; Drewes AM; Olesen AE
[Ad] Address:Mech-Sense, Department of Gastroenterology and Hepatology, Aalborg University Hospital, Aalborg, Denmark; Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
[Ti] Title:The impact of naloxegol on anal sphincter function - Using a human experimental model of opioid-induced bowel dysfunction.
[So] Source:Eur J Pharm Sci;117:187-192, 2018 Feb 09.
[Is] ISSN:1879-0720
[Cp] Country of publication:Netherlands
[La] Language:eng
[Ab] Abstract:BACKGROUND AND AIMS: Opioid treatment interferes with anal sphincter function and its regulation during defecation. This may result in straining, incomplete evacuation, and contribute to opioid-induced bowel dysfunction (OIBD). Employing an experimental model of oxycodone-induced OIBD, we hypothesized that co-administration of the peripherally acting µ-opioid antagonist naloxegol would improve anal sphincter function in comparison to placebo. METHODS: In a double-blind randomized crossover trial, 24 healthy males were assigned to a six-day treatment of oral oxycodone 15 mg twice daily in combination with either oral naloxegol 25 mg once daily or placebo. At baseline and at day 6, anal resting pressure and the recto-anal inhibitory reflex (RAIR) were evaluated using manometry and rectal balloon distension. Furthermore, the functional lumen imaging probe was used to measure distensibility of the anal canal. Gastrointestinal symptoms were assessed with the Patient Assessment of Constipation Symptom (PAC-SYM) questionnaire and the Bristol Stool Form Scale. RESULTS: During oxycodone treatment, naloxegol improved RAIR-induced sphincter relaxation by 15% (-45.9 vs -38.8 mm Hg; P < 0.01). No differences in anal resting pressure and anal canal distensibility were found between treatments (all P > 0.5). Naloxegol improved PAC-SYM symptoms (mean score over days; 2.6 vs 4.5, P < 0.001) and improved stool consistency scores (mean score over days; 3.3 vs 2.9, P < 0.01). CONCLUSIONS: In this experimental model of OIBD, naloxegol improved the RAIR and reduced gastrointestinal symptoms. Hence, in contrast to conventional laxatives, naloxegol may regulate opioid-induced anal sphincter dysfunction and facilitate the defecation process.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1802
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  7 / 138254 MEDLINE  
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[PMID]: 29331677
[Au] Autor:Montelius M; Spetz J; Jalnefjord O; Berger E; Nilsson O; Ljungberg M; Forssell-Aronsson E
[Ad] Address:Department of Radiation Physics, Institute of Clinical Sciences, Sahlgrenska Cancer Center, Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: mikael.montelius@radfys.gu.se.
[Ti] Title:Identification of Potential MR-Derived Biomarkers for Tumor Tissue Response to Lu-Octreotate Therapy in an Animal Model of Small Intestine Neuroendocrine Tumor.
[So] Source:Transl Oncol;11(2):193-204, 2018 Jan 11.
[Is] ISSN:1936-5233
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Magnetic resonance (MR) methods enable noninvasive, regional tumor therapy response assessment, but associations between MR parameters, underlying biology, and therapeutic effects must be investigated. The aim of this study was to investigate response assessment efficacy and biological associations of MR parameters in a neuroendocrine tumor (NET) model subjected to radionuclide treatment. Twenty-one mice with NETs received Lu-octreotate at day 0. MR experiments (day -1, 1, 3, 8, and 13) included T2-weighted, dynamic contrast-enhanced (DCE) and diffusion-weighted imaging (DWI) and relaxation measurements (T1/T2*). Tumor tissue was analyzed using proteomics. MR-derived parameters were evaluated for each examination day and for different radial distances from the tumor center. Response assessment efficacy and biological associations were evaluated using feature selection and protein expression correlations, respectively. Reduced tumor growth rate or shrinkage was observed until day 8, followed by reestablished growth in most tumors. The most important MR parameter for response prediction was DCE-MRI-derived pretreatment signal enhancement ratio (SER) at 40% to 60% radial distance, where it correlated significantly also with centrally sampled protein CCD89 (association: DNA damage and repair, proliferation, cell cycle arrest). The second most important was changed diffusion (D) between day -1 and day 3, at 60% to 80% radial distance, where it correlated significantly also with peripherally sampled protein CATA (association: oxidative stress, proliferation, cell cycle arrest, apoptotic cell death). Important information regarding tumor biology in response to radionuclide therapy is reflected in several MR parameters, SER and D in particular. The spatial and temporal information provided by MR methods increases the sensitivity for tumor therapy response.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1801
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  8 / 138254 MEDLINE  
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[PMID]: 29278836
[Au] Autor:Chaney ME; Dao TV; Brechtel BS; Belovich SJ; Siesel KJ; Fredieu JR
[Ad] Address:Department of Anthropology & School of Biomedical Sciences, Kent State University, Kent, OH, United States. Electronic address: mchaney1@kent.edu.
[Ti] Title:The fibularis digiti quinti tendon: A cadaveric study with anthropological and clinical considerations.
[So] Source:Foot (Edinb);34:45-47, 2017 Dec 05.
[Is] ISSN:1532-2963
[Cp] Country of publication:Scotland
[La] Language:eng
[Ab] Abstract:In addition to the fibularis longus and brevis muscles, a number of anomalous muscles or tendons can arise from the lateral compartment of the leg. The authors describe a bilateral and robust fibularis digiti quinti (FDQ) tendon present in the foot of a 99-year-old female cadaver, present the incidence of this tendon in a cohort of 26 cadavers dissected by podiatric-medical students for a lower-extremity anatomy course, and discuss the anthropological and clinical significance of the findings. In these specimen, the FDQ tendon arose from the fibularis brevis tendon proximal to the lateral malleolus, but did not separate completely from the fibularis brevis tendon until passing through the inferior fibular retinaculum. On the lateral dorsum of the foot, the FDQ passed through a third fibular retinaculum formed by the fibularis tertius tendon, and inserted onto the extensor sling of the fifth digit. This case specimen is designated as an example of the fully present category. Of the 52 limbs dissected, 17 limbs (33%) showed a fully present FDQ, while 20 limbs (38%) exhibited an FDQ in a rudimentary form. Thus, 71% of the limbs showed some presence of the FDQ. Because human bipedality requires less dexterity than that of nonhuman primates in the routine use of their hindlimbs, the authors interpret the high variability of the FDQ, including its absence in many feet, as a relaxation of natural selection maintaining this trait since the divergence of humans from African apes.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1712
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher

  9 / 138254 MEDLINE  
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[PMID]: 29523857
[Au] Autor:Woost L; Bazin PL; Taubert M; Trampel R; Tardif CL; Garthe A; Kempermann G; Renner U; Stalla G; Ott DVM; Rjosk V; Obrig H; Villringer A; Roggenhofer E; Klein TA
[Ad] Address:Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany. mendil@cbs.mpg.de.
[Ti] Title:Physical Exercise and Spatial Training: A Longitudinal Study of Effects on Cognition, Growth Factors, and Hippocampal Plasticity.
[So] Source:Sci Rep;8(1):4239, 2018 Mar 09.
[Is] ISSN:2045-2322
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Physical exercise has been suggested to improve cognitive performance through various neurobiological mechanisms, mediated by growth factors such as BDNF, IGF-I, and VEGF. Moreover, animal research has demonstrated that combined physical and cognitive stimulation leads to increased adult neurogenesis as compared to either experimental condition alone. In the present study, we therefore investigated whether a sequential combination of physical and spatial training in young, healthy adults elicits an additive effect on training and transfer gains. To this end, we compared the effects of (i) eight 20-minute sessions of cycling, (ii) sixteen 30-minute sessions of spatial training, (iii) a combination of both, and included (iv) a passive control cohort. We assessed longitudinal changes in cognitive performance, growth factor levels, and T relaxation of hippocampal subfields (acquired with 7 T MRI). While substantial physical and spatial training gains were elicited in all trained groups, longitudinal transfer changes did not differ between these groups. Notably, we found no evidence for an additive effect of sequential physical and spatial training. These results challenge the extrapolation from the findings reported in animals to young, healthy adults.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:In-Data-Review
[do] DOI:10.1038/s41598-018-19993-9

  10 / 138254 MEDLINE  
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[PMID]: 29496627
[Au] Autor:Nadein K; Betz O
[Ad] Address:Senckenberg German Entomological Institute, Eberswalder Str. 90, 15374, Müncheberg, Germany. Electronic address: k.nadein@gmail.com.
[Ti] Title:Jumping mechanisms and performance in beetles. II. Weevils (Coleoptera: Curculionidae: Rhamphini).
[So] Source:Arthropod Struct Dev;, 2018 Mar 06.
[Is] ISSN:1873-5495
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:We describe the kinematics and performance of the natural jump in the weevil Orchestes fagi (Fabricius, 1801) (Coleoptera: Curculionidae) and its jumping apparatus with underlying anatomy and functional morphology. In weevils, jumping is performed by the hind legs and involves the extension of the hind tibia. The principal structural elements of the jumping apparatus are (1) the femoro-tibial joint, (2) the metafemoral extensor tendon, (3) the extensor ligament, (4) the flexor ligament, (5) the tibial flexor sclerite and (6) the extensor and flexor muscles. The kinematic parameters of the jump (from minimum to maximum) are 530-1965 m s (acceleration), 0.7-2.0 m s (velocity), 1.5-3.0 ms (time to take-off), 0.3-4.4 µJ (kinetic energy) and 54-200 (g-force). The specific joint power as calculated for the femoro-tibial joint during the jumping movement is 0.97 W g . The full extension of the hind tibia during the jump was reached within up to 1.8-2.5 ms. The kinematic parameters, the specific joint power and the time for the full extension of the hind tibia suggest that the jump is performed via a catapult mechanism with an input of elastic strain energy. A resilin-bearing elastic extensor ligament that connects the extensor tendon and the tibial base is considered to be the structure that accumulates the elastic strain energy for the jump. According to our functional model, the extensor ligament is loaded by the contraction of the extensor muscle, while the co-contraction of the antagonistic extensor and flexor muscles prevents the early extension of the tibia. This is attributable to the leverage factors of the femoro-tibial joint providing a mechanical advantage for the flexor muscles over the extensor muscles in the fully flexed position. The release of the accumulated energy is performed by the rapid relaxation of the flexor muscles resulting in the fast extension of the hind tibia propelling the body into air.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1803
[Cu] Class update date: 180310
[Lr] Last revision date:180310
[St] Status:Publisher


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