Grant's gazelles have recently been proposed to be a species complex comprising three highly divergent mtDNA lineages (Nanger granti, N. notata and N. petersii). The three lineages have ...nonoverlapping distributions in East Africa, but without any obvious geographical divisions, making them an interesting model for studying the early‐stage evolutionary dynamics of allopatric speciation in detail. Here, we use genomic data obtained by restriction site‐associated (RAD) sequencing of 106 gazelle individuals to shed light on the evolutionary processes underlying Grant's gazelle divergence, to characterize their genetic structure and to assess the presence of gene flow between the main lineages in the species complex. We date the species divergence to 134,000 years ago, which is recent in evolutionary terms. We find population subdivision within N. granti, which coincides with the previously suggested two subspecies, N. g. granti and N. g. robertsii. Moreover, these two lineages seem to have hybridized in Masai Mara. Perhaps more surprisingly given their extreme genetic differentiation, N. granti and N. petersii also show signs of prolonged admixture in Mkomazi, which we identified as a hybrid population most likely founded by allopatric lineages coming into secondary contact. Despite the admixed composition of this population, elevated X chromosomal differentiation suggests that selection may be shaping the outcome of hybridization in this population. Our results therefore provide detailed insights into the processes of allopatric speciation and secondary contact in a recently radiated species complex.
Background A high percentage of female athletes who sustain an anterior cruciate ligament (ACL) rupture suffer serious long-term consequences
such as osteoarthritis and disability. Thus, ...identification of risk factors has high clinical relevance in the prevention
of ACL rupture.
Hypothesis Noninjured athletes with low knee flexor electromyography (EMG) preactivity and high knee extensor EMG preactivity during
sidecutting are at increased risk of future ACL rupture.
Study Design Cohort study (prognosis); Level of evidence, 2.
Methods Fifty-five elite female athletes (team handball and soccer) aged 24 ± 5 years with no history of ACL injury were tested for
EMG preactivity of vastus lateralis and medialis, rectus femoris, semitendinosus, and biceps femoris during a standardized
side-cutting maneuver. The incidence of ACL ruptures was registered in the following 2 match seasons.
Results During the subsequent 2 match seasons, 5 athletes sustained a confirmed noncontact ACL rupture. Before injury, all 5 players
displayed a neuromuscular pattern that differed from the noninjured players, characterized by reduced EMG preactivity for
the semitendinosus (ST) and elevated EMG preactivity for the vastus lateralis (VL) ( P < .01). On the basis of these findings, a high-risk zone was defined as one standard deviation above the mean VL-ST difference.
In our population, 5 of 10 subjects with a VL-ST difference in this zone sustained an ACL injury during the study period.
Conclusion In the present study, currently noninjured female athletes with reduced EMG preactivity of the ST and increased EMG preactivity
of the VL during side cutting were at increased risk of future noncontact ACL rupture. Our data indicate that a high-risk
zone can be used to identify noninjured players at high risk of future ACL rupture. Consequently, individual preventive efforts
can be introduced in time. However, large prospective studies are needed to confirm this finding before definitive clinical
recommendations can be made.
The Image as a Living Atlas in the World. An Introduction to George Didi-Huberman’s Image Theory Project and Curatorial PracticeThis article delivers both an overview of the ongoing work of art ...historian Georges Didi-Huberman (b. 1953) and an attempt at analyzing the incarnational conception of images that runs through Didi-Huberman’s image theory. In the Christian tradition, images are the result of an incarnational double-economy. Didi-Huberman’s early interpretations in Fra Angelico, dissemblance et figuration are central to our understanding of this incarnational economy. The visible is capable of entering our flesh; to control this incarnational invasion, Christian tradition has developed a reflexive capacity to read these invasions as images in acts of exegesis. This reflexive exegetical economy is pivotal for Didi-Huberman’s political position regarding our modern use and abuse of images. Confronted with Pier Paolo Pasolini’s conviction that we live in a fascistic state of emergency that blinds our senses with total illumination, Didi-Huberman insists in believing that the described reflexive double-economy is still enabling us to let the visible enter our bodies and light up the darkness of our flesh from within as images – thereby developing our imagination and freeing us from the deadening total image that is fascism.
Sports Medicine Research Unit, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg, Copenhagen, Denmark
Kjær, Michael. Role of Extracellular Matrix in Adaptation of Tendon and ...Skeletal Muscle to Mechanical Loading. Physiol Rev 84: 649698, 2004; 10.1152/physrev.00031.2003.The extracellular matrix (ECM), and especially the connective tissue with its collagen, links tissues of the body together and plays an important role in the force transmission and tissue structure maintenance especially in tendons, ligaments, bone, and muscle. The ECM turnover is influenced by physical activity, and both collagen synthesis and degrading metalloprotease enzymes increase with mechanical loading. Both transcription and posttranslational modifications, as well as local and systemic release of growth factors, are enhanced following exercise. For tendons, metabolic activity, circulatory responses, and collagen turnover are demonstrated to be more pronounced in humans than hitherto thought. Conversely, inactivity markedly decreases collagen turnover in both tendon and muscle. Chronic loading in the form of physical training leads both to increased collagen turnover as well as, dependent on the type of collagen in question, some degree of net collagen synthesis. These changes will modify the mechanical properties and the viscoelastic characteristics of the tissue, decrease its stress, and likely make it more load resistant. Cross-linking in connective tissue involves an intimate, enzymatical interplay between collagen synthesis and ECM proteoglycan components during growth and maturation and influences the collagen-derived functional properties of the tissue. With aging, glycation contributes to additional cross-linking which modifies tissue stiffness. Physiological signaling pathways from mechanical loading to changes in ECM most likely involve feedback signaling that results in rapid alterations in the mechanical properties of the ECM. In developing skeletal muscle, an important interplay between muscle cells and the ECM is present, and some evidence from adult human muscle suggests common signaling pathways to stimulate contractile and ECM components. Unaccostumed overloading responses suggest an important role of ECM in the adaptation of myofibrillar structures in adult muscle. Development of overuse injury in tendons involve morphological and biochemical changes including altered collagen typing and fibril size, hypervascularization zones, accumulation of nociceptive substances, and impaired collagen degradation activity. Counteracting these phenomena requires adjusted loading rather than absence of loading in the form of immobilization. Full understanding of these physiological processes will provide the physiological basis for understanding of tissue overloading and injury seen in both tendons and muscle with repetitive work and leisure time physical activity.
Address for reprint requests and other correspondence: M. Kjær, Sports Medicine Research Unit, Dept. of Rheumatology, Copenhagen University Hospital at Bispebjerg, 23 Bispebjerg Bakke, DK-2400 Copenhagen NV, Denmark (E-mail: m.kjaer{at}mfi.ku.dk ).
The majority of young women use oral contraceptives (OCs). Use of OCs has been associated with lower myofibrillar protein and tendon collagen synthesis rates, but it is unknown whether OCs will limit ...the adaptive response of myotendinous tissue to resistance training.
Fourteen healthy untrained young regular OC users (24 ± 1 years, fat% 32 ± 1, 35 ± 2 ml⋅min
⋅kg
) and 14 NOC users (non-OC, controls) (24 ± 1 years, fat% 32 ± 2, 34 ± 2 ml⋅min
⋅kg
) performed a 10-week supervised lower extremity progressive resistance training program. Before and after the intervention biopsies from the vastus lateralis muscle and the patellar tendon were obtained. Muscle (quadriceps) and tendon cross-sectional area (CSA) was determined by magnetic resonance imaging (MRI) scans, and muscle fiber CSA was determined by histochemistry. Maximal isometric knee extension strength was assessed by dynamometry while 1 repetition maximum (RM) was determined during knee extension.
Training enhanced CSA in both muscle (
< 0.001) and tendon (
< 0.01). A trend toward a greater increase in muscle CSA was observed for OC (11%) compared to NOC (8%) (interaction
= 0.06). Analysis of mean muscle fiber type CSA showed a trend toward an increase in type II muscle fiber area in both groups (
= 0.11, interaction
= 0.98), whereas type I muscle fiber CSA increased in the OC group (
= 9, 3821 ± 197 to 4490 ± 313 mm
,
< 0.05), but not in NOC (
= 7, 4020 ± 348 to 3777 ± 354 mm
,
= 0.40) (interaction
< 0.05).
analyses indicated that the effect of OCs on muscle mass increase was induced by the OC-users (
= 7), who used OCs containing 30 μg ethinyl estradiol (EE), whereas the response in users taking OCs with 20 μg EE (
= 7) did not differ from NOC. Both the OC and NOC group experienced an increase in maximal knee strength (
< 0.001) and 1RM leg extension (
< 0.001) after the training period with no difference between groups.
Use of OCs during a 10-week supervised progressive resistance training program was associated with a trend toward a greater increase in muscle mass and a significantly greater increase in type I muscle fiber area compared to controls. Yet, use of OCs did not influence the overall increase in muscle strength related to training.
Muscle after spinal cord injury Biering-Sørensen, Bo; Kristensen, Ida Bruun; Kjær, Michael ...
Muscle & nerve,
October 2009, Letnik:
40, Številka:
4
Journal Article
Recenzirano
The morphological and contractile changes of muscles below the level of the lesion after spinal cord injury (SCI) are dramatic. In humans with SCI, a fiber‐type transformation away from type I begins ...4–7 months post‐SCI and reaches a new steady state with predominantly fast glycolytic IIX fibers years after the injury. There is a progressive drop in the proportion of slow myosin heavy chain (MHC) isoform fibers and a rise in the proportion of fibers that coexpress both the fast and slow MHC isoforms. The oxidative enzymatic activity starts to decline after the first few months post‐SCI. Muscles from individuals with chronic SCI show less resistance to fatigue, and the speed‐related contractile properties change, becoming faster. These findings are also present in animals. Future studies should longitudinally examine changes in muscles from early SCI until steady state is reached in order to determine optimal training protocols for maintaining skeletal muscle after paralysis. Muscle Nerve, 2009
The present study investigated the influence of creatine and protein supplementation on satellite cell frequency and number
of myonuclei in human skeletal muscle during 16 weeks of heavy-resistance ...training. In a double-blinded design 32 healthy,
male subjects (19â26 years) were assigned to strength training (STR) while receiving a timed intake of creatine (STR-CRE)
( n
= 9), protein (STR-PRO) ( n
= 8) or placebo (STR-CON) ( n
= 8), or serving as a non-training control group (CON) ( n
= 7). Supplementation was given daily (STR-CRE: 6â24 g creatine monohydrate, STR-PRO: 20 g protein, STR-CON: placebo).
Furthermore, timed protein/placebo intake were administered at all training sessions. Muscle biopsies were obtained at week
0, 4, 8 (week 8 not CON) and 16 of resistance training (3 days per week). Satellite cells were identified by immunohistochemistry.
Muscle mean fibre (MFA) area was determined after histochemical analysis. All training regimes were found to increase the
proportion of satellite cells, but significantly greater enhancements were observed with creatine supplementation at week
4 (compared to STR-CON) and at week 8 (compared to STR-PRO and STR-CON) ( P < 0.01â0.05). At week 16, satellite cell number was no longer elevated in STR-CRE, while it remained elevated in STR-PRO
and STR-CON. Furthermore, creatine supplementation resulted in an increased number of myonuclei per fibre and increases of
14â17% in MFA at week 4, 8 and 16 ( P < 0.01). In contrast, STR-PRO showed increase in MFA only in the later (16 week, +8%) and STR-CON only in the early (week
4, +14%) phases of training, respectively ( P < 0.05). In STR-CRE a positive relationship was found between the percentage increases in MFA and myonuclei from baseline
to week 16, respectively ( r
= 0.67, P < 0.05). No changes were observed in the control group (CON). In conclusion, the present study demonstrates for the first
time that creatine supplementation in combination with strength training amplifies the training-induced increase in satellite
cell number and myonuclei concentration in human skeletal muscle fibres, thereby allowing an enhanced muscle fibre growth
in response to strength training.
Treatment with lipid-lowering drugs, statins, is common all over the world. Lately, the occurrence of spontaneous tendon ruptures or tendinosis have suggested a negative influence of statins upon ...tendon tissue. But how statins might influence tendons is not clear. In the present study, we investigated the effect of statin treatment on mechanical strength, cell proliferation, collagen content and gene expression pattern in a tendon-like tissue made from human tenocytes in vitro. Human tendon fibroblasts were grown in a 3D tissue culture model (tendon constructs), and treated with either simvastatin or atorvastatin, low or high dose, respectively, for up to seven days. After seven days of treatment, mechanical testing of the constructs was performed. Collagen content and cell proliferation were also determined. mRNA levels of several target genes were measured after one or seven days. The maximum force and stiffness were reduced by both statins after 7 days (p<0.05), while the cross sectional area was unaffected. Further, the collagen content was reduced by atorvastatin (p = 0.01) and the cell proliferation rate was decreased by both types of statins (p<0.05). Statin treatment also introduced increased mRNA levels of MMP-1, MMP-3, MMP-13, TIMP-1 and decreased levels of collagen type 1 and 3. In conclusion, statin treatment appears to have a negative effect on tendon matrix quality as seen by a reduced strength of the tendon constructs. Further, activated catabolic changes in the gene expression pattern and a reduced collagen content indicated a disturbed balance in matrix production of tendon due to statin administration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Tendons are vital collagen-dense specialized connective tissues transducing the force from skeletal muscle to the bone, thus enabling movement of the human body. Tendon cells adjust matrix turnover ...in response to physiological tissue loading and pathological overloading (tendinopathy). Nevertheless, the regulation of tendon matrix quality control is still poorly understood and the pathogenesis of tendinopathy is presently unsolved. Autophagy, the major mechanism of degradation and recycling of cellular components, plays a fundamental role in the homeostasis of several tissues. Here, we investigate the contribution of autophagy to human tendons' physiology, and we provide in vivo evidence that it is an active process in human tendon tissue. We show that selective autophagy of the endoplasmic reticulum (ER-phagy), regulates the secretion of type I procollagen (PC1), the major component of tendon extracellular matrix. Pharmacological activation of autophagy by inhibition of mTOR pathway alters the ultrastructural morphology of three-dimensional tissue-engineered tendons, shifting collagen fibrils size distribution. Moreover, autophagy induction negatively affects the biomechanical properties of the tissue-engineered tendons, causing a reduction in mechanical strength under tensile force. Overall, our results provide the first evidence that autophagy regulates tendon homeostasis by controlling PC1 quality control, thus potentially playing a role in the development of injured tendons.
Immobilization of the lower limbs promotes a catabolic state that reduces muscle mass, whereas physical training promotes an anabolic state that increases muscle mass. Understanding the molecular ...mechanisms underlying this is of clinical interest, as loss of muscle mass is a major complication to critical illness in humans. To determine the molecular regulation of protein synthesis and degradation during muscle loss and hypertrophy, we examined skeletal muscle biopsies from healthy human subjects after 2 weeks unilateral immobilization of a lower limb and during 6 weeks of physical rehabilitation. We have previously shown that cross-sectional area of the knee muscle-extensors decreased by ∼10% during immobilization and was completely restored during rehabilitation. Here we provide novel data to suggest that autophagy is an important underlying mechanism involved in regulation of muscle mass. Protein expression of MuRF1 and ATROGIN-1 did not change during the study, indicating that the recruitment of substrates to the proteasomes was unaltered. Phosphorylation of mTORat Ser
did not change during the study, and neither did phosphorylation of the mTORC1 substrates 4EBP1 Thr
and p70S6K Thr
, suggesting that this pathway does not suppress protein synthesis during muscle wasting. Protein levels of p62 and ULK1 increased during immobilization and returned to baseline levels during rehabilitation. Same pattern was observed for FOXO3a phosphorylation at Ser
, suggesting transcriptional activation during immobilization and inactivation during rehabilitation. To investigate this further, we analyzed mRNA expression of seven autophagy-related genes controlled by FOXO3a. Five of these (p62, LC3B, BECLIN-1, ATG12, and BNIP3) increased during immobilization and returned to baseline during rehabilitation. In conclusion, immobilization of a lower limb increases autophagy-related gene and protein expression in human skeletal muscle in a pattern that mirrors FOXO3a phosphorylation. These findings could imply that FOXO3a dependent transcriptional regulation of autophagy is involved in the regulation of muscle mass in humans.
The study was approved by the Ethics Committee of Copenhagen (j.no. H-1-2010-016).
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