Reduced activity of BRAF protein kinase in hop and hop(hpy) mouse mutants.
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Animals↗
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Models of hopping-controlled reactions with variable hopping range.
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Journal Article↗
Hop on, hop off routes.
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Education, Nursing, Baccalaureate↗
[Problems of the work hygiene of hop growers in the manual harvesting and drying of the hops].
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Agriculture↗
[The sedative-hypnotic action of hops. 4. Pharmacology of the hop substance 2-methyl-3-buten-2-ol].
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Animals↗
A test battery for evaluating hop performance in patients with an ACL injury and patients who have undergone ACL reconstruction.
The purpose of this study was to develop a test battery of hop tests with high ability to discriminate (i.e. high test-retest reliability, sensitivity, specificity and accuracy) between the hop performance of the injured and the uninjured side in patients with an ACL injury and in patients who have undergone ACL reconstruction. Five hop tests were analysed: three maximum single hop tests and two hop tests while developing fatigue. Fifteen healthy subjects performed the five hop tests on three separate occasions in a test-retest design. Thirty patients, mean 11 months after an ACL injury and 35 patients, mean 6 months after ACL reconstruction were tested. ICC values ranged from 0.85 to 0.97 for the five hop tests, indicating that all the tests had high test-retest reliability. Sixty-seven percent to 100% of the healthy subjects had normal symmetry (i.e. <10% side-to-side difference) in the five hop tests. Abnormal symmetry in the five hop tests ranged from 43 to 77% for patients with an ACL injury and from 51 to 86% for patients who had undergone ACL reconstruction respectively. The three tests with the highest ability to discriminate hop performance were chosen for the test battery; they were the vertical jump, the hop for distance and the side hop. The test battery revealed a high level of sensitivity and accuracy in patients with an ACL injury (87 and 84%) and in patients who had undergone ACL reconstruction (91 and 88%), when at least one of the three tests was classified as abnormal. To summarise, the test battery consisting of both maximum single hop performances: the vertical jump and the hop for distance and hop performance while developing fatigue: the side hop, produced high test-retest reliability, sensitivity and accuracy. Further, the test battery produced higher values compared with any of the three hop tests individually revealing that only one out of ten patients had restored hop performance 11 months after an ACL injury and 6 months after ACL reconstruction. It is concluded that this test battery showed a high ability to discriminate between the hop performance of the injured and the uninjured side both in patients with an ACL injury and in patients who have undergone ACL reconstruction.
Adult↗
Test-retest reliability of 4 single-leg horizontal hop tests.
The purpose of this study was to determine the test-retest reliability of 4 single-leg horizontal hop tests (i.e., single hop for distance, triple hop for distance, crossover hop for distance, and 6-m hop for time), with a time interval of approximately 4 weeks separating the 2 testing sessions. Eighteen healthy, young, adult men, all cadets enrolled at the U.S. Air Force Academy, Colorado, performed the single hop for distance, the triple hop for distance, the crossover hop for distance, and the 6-m hop for time during 2 testing sessions separated by 31.2 +/- 0.4 days. Reliability data for each of the single-leg hop tests were studied through a repeated measures analysis of variance, intraclass correlation coefficients (ICCs), and standard errors of measurement (SEMs). The ICCs ranged from 0.92 to 0.97 for the 4 single-leg hop tests. The SEMs for the single-leg hop tests that assessed the distance hopped ranged from 4.61 to 17.74 cm. The SEM for the 6-m hop for time test was 0.06 seconds. No significant differences were noted when the mean scores of the 2 test trials were compared by a repeated measures analysis of variance for any of the single-leg hop tests. These results indicate that the single-leg hop tests examined in this study offer strength and conditioning professionals a reliable method to assess the single-leg horizontal hopping capabilities of healthy, young, adult men, with intervals of approximately 4 weeks between testing sessions.
Adult↗
Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro.
We reported previously that a 32-36-kDa osteogenic protein purified from bovine bone matrix is composed of dimers of two members of the transforming growth factor (TGF)-beta superfamily: the bovine equivalent of human osteogenic protein-1 (OP-1) and bone morphogenetic protein-2a, BMP-2a (BMP-2). In the present study, we produced the recombinant human OP-1 (hOP-1) in mammalian cells as a processed mature disulfide-linked homodimer with an apparent molecular weight of 36,000. Examination of hOP-1 in the rat subcutaneous bone induction model demonstrated that hOP-1 was capable of inducing new bone formation with a specific activity comparable with that exhibited by highly purified bovine osteogenic protein preparations. The half-maximal bone-inducing activity of hOP-1 in combination with a rat collagen matrix preparation was 50-100 ng/25 mg of matrix as determined by the calcium content of day 12 implants. Evaluation of hOP-1 effects on cell growth and collagen synthesis in rat osteoblast-enriched bone cell cultures showed that both cell proliferation and collagen synthesis were stimulated in a dose-dependent manner and increased 3-fold in response to 40 ng of hOP-1/ml. Examination of the expression of markers characteristic of the osteoblast phenotype showed that hOP-1 specifically stimulated the induction of alkaline phosphatase (4-fold increase at 40 ng of hOP-1/ml), parathyroid hormone-mediated intracellular cAMP production (4-fold increase at 40 ng of hOP-1/ml), and osteocalcin synthesis (5-fold increase at 25 ng of hOP-1/ml). In long-term (11-17 day) cultures of osteoblasts in the presence of beta-glycerophosphate and L(+)-ascorbate, hOP-1 markedly increased the rate of mineralization as measured by the number of mineral nodules per well (20-fold increase at 20 ng of hOP-1/ml). Direct comparison of TGF-beta 1 and hOP-1 in these bone cell cultures indicated that, although both hOP-1 and TGF-beta 1 promoted cell proliferation and collagen synthesis, only hOP-1 was effective in specifically stimulating markers of the osteoblast phenotype.
Alkaline Phosphatase↗
Biochemical characterization of horA-independent hop resistance mechanism in Lactobacillus brevis.
We isolated a strain from hop-resistant Lactobacillus hrevis ABBC45, which had lost a plasmid (pRH45) harboring a putative hop resistance gene, horA. The hop resistance level of this horA-deficient strain, named ABBC45(C), was initially low but gradually induced by repeated growth in media containing progressively increasing levels of hop compounds. Although the hop resistance level was substantially lower than that of the hop-adapted wild type strain, hop-adapted ABBC45(C) (ABBC45(CR)) was still capable of growing in beer, suggesting ABBC45 possesses at least two hop resistance mechanisms. Hop resistance acquired by ABBC45(CR) gradually diminished to the pre-adapted level, when the strain was grown repeatedly in the absence of hop compounds. ABBC45(CR) was found to be cross-resistant to several structurally unrelated drugs, including ethidium bromide, daunomycin and nisin. In addition, ABBC45(CR) was shown to extrude ethidium in an energy-dependent manner, while ABBC45(C) did not show such activity. This indicates that the efflux pump was induced by adaptation to hop compounds. The efflux activity of ethidium was reduced by the addition of hop compounds, suggesting hop compounds are also the substrate of the efflux pump. It was also shown that the efflux activity was completely dissipated with the abolition of proton motive force (PMF). These results, taken together, suggest the hop resistance mechanism of ABBC45(C) is mediated by PMF-dependent multidrug efflux pump.
Beer↗
Hop modulates Hsp70/Hsp90 interactions in protein folding.
Hop is a 60-kDa protein characterized by its ability to bind the two chaperones, hsp70 and hsp90. We have tested the function of Hop using an assay for the refolding of denatured firefly luciferase. We show that Hop is involved in the process of refolding thermally denatured firefly luciferase in rabbit reticulocyte lysate. Hop also stimulates refolding by hsp70 and Ydj-1 in a purified refolding system. Hsp90 can also stimulate refolding, and optimal refolding is observed in the presence of both Hop and hsp90. Similar stimulation was observed when Hop was replaced by its yeast homolog Sti1. In assays of the binding of Hop to hsp70 and hsp90, Hop preferentially forms a complex with ADP-bound hsp70, and this process is unaffected by the presence of hsp90. Hop does not alter the ATPase activity or the rate of ADP dissociation of hsp70. Hop also appears to bind to the ADP-bound form of hsp90, blocking the ATP-dependent conversion of hsp90 to a form capable of interacting with p23. Conversely, once p23 is bound to hsp90, Hop binding is diminished. These results confirm that Hop provides a physical link between hsp70 and hsp90 and also indicate that Hop modulates the activities of both of these chaperone proteins.
Adenosine Diphosphate↗
Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7).
We examined the efficacy of a single application of recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7) for its ability to regenerate large calvarial defects in adult male baboons (Papio ursinus). Recombinant hOP-1, in conjunction with baboon or bovine guanidinium-extracted insoluble collagenous bone matrix (0.1, 0.5 and 2.5 mg per g of collagenous matrix as carrier), was implanted in 46 calvarial defects surgically prepared in 14 baboons, whilst 18 defects were implanted with the carrier matrix without hOP-1. Specimens were harvested on d 15, 30, 90 and 365 and subjected to histomorphometry on serial undecalcified sections cut at 7 microm to study the temporal sequence of tissue morphogenesis after the single application of hOP-1. Histological analysis indicated that the induction of new bone formation proceeded from the periphery to the central core of hOP-1 treated specimens after rapid angiogenesis and mesenchymal cell migration in apposition to the collagenous matrix. Whilst chondrogenesis was limited, newly formed bone has already filled with fully differentiated bone marrow elements as early as d 15, even with the 0.1 mg dose of hOP-1. On d 30 and 90, doses of 0.1 and 0.5 mg of hOP-1 showed greater amounts of bone than controls, and on d 90, they induced complete regeneration of the defects. Doses of 2.5 mg hOP-1 per g of matrix induced extensive osteogenesis initially with heterotopic ossification and displacement of the temporalis muscle above the defects. One year after implantation of hOP-1 there was restoration of the internal and external cortices of the calvaria. These results show that hOP-1 induces complete regeneration of calvarial bone in the adult primate, and suggest that the optimal activity of hOP-1 to achieve regeneration is between 100 and 500 microg of hOP-1 per g of matrix. These results in the primate may form the scientific basis for future clinical applications of hOP-1.
Animals↗
Patterns of muscle activation in human hopping.
In the present study, we examined the electromyogram (EMG) patterns of the soleus and medial gastrocnemius (MG) muscles during rhythmical, two-legged hopping to investigate the contributions of the monosynaptic short- and long-latency stretch reflexes during such a natural movement in human. During rhythmical hopping, soleus muscle is activated reflexly at near-monosynaptic latency by stretch resulting from passive ankle flexion upon landing. Soleus muscle also contracts voluntarily in order to launch the body into the next hop. This is part of the rhythmical bursts of activity producing the hops. Depending on the hopping interval, this phase of activation can follow the short-latency phase or precede landing at very short hopping intervals. In MG, there is an initial phase of activity that stiffens the muscle in preparation for landing, and continues through the contact phase. The monosynaptic reflex response to landing is usually superimposed on this activity. Depending on the hopping interval, both of these responses may be overlaid with activity that is time-locked to the take-off into the next hop, and serves to launch the body into the next hop. However, no evidence for a long-latency stretch reflex was found. In addition, the preferred hopping frequency for all subjects was about 2 Hz. This frequency is associated with a pattern of EMG activity the timing of which indicates that it balances the requirement for a comfortable landing from a hop with the optimal muscle activation required for launching the following hop.
Adult↗
Single-leg hop testing following fatiguing exercise: reliability and biomechanical analysis.
A fatiguing exercise protocol was combined with single-leg hop testing to improve the possibilities of evaluating the effects of training or rehabilitation interventions. In the first test-retest experiment, 11 healthy male subjects performed two trials of single-leg hops under three different test conditions: non-fatigued and following fatiguing exercise, which consisted of unilateral weight machine knee extensions at 80% and 50%, respectively, of 1 repetition maximum (1 RM) strength. Intraclass correlation coefficients ranged from 0.75 to 0.98 for different hop test conditions, indicating that all tests were reliable. For the second experiment, eight healthy male subjects performed the fatiguing exercise protocol to investigate how fatigue influences lower-extremity joint kinematics and kinetics during single-leg hops. Hip, knee and ankle joint angles, moments and powers, as well as ground-reaction forces were recorded with a six-camera, motion-capture system and a force platform. Recovery of hop performance following the fatiguing exercise was also measured. During the take-off for the single-leg hops, hip and knee flexion angles, generated powers for the knee and ankle joints, and ground-reaction forces decreased for the fatigued hop conditions compared with the non-fatigued condition (P<0.05). Compared with landing during the non-fatigued condition, hip moments and ground-reaction forces were lower for the fatigued hop conditions (P<0.05). The negative joint power was two to three times greater for the knee than for the hip and five to 10 times greater for the knee than for the ankle during landing for all test conditions (P<0.05). Most measured variables had recovered three minutes post-exercise. It is concluded that the fatiguing exercise protocol combined with single-leg hop testing was a reliable method for investigating functional performance under fatigued test conditions. Further, subjects utilized an adapted hop strategy, which employed less hip and knee flexion and generated powers for the knee and ankle joints during take-off, and less hip joint moments during landing under fatigued conditions. The large negative power values observed at the knee joint during the landing phase of the single-leg hop, during which the quadriceps muscle activates eccentrically, indicate that not only hop distance but also the ability to perform successful landings should be investigated when assessing dynamic knee function.
Adult↗
Leg stiffness primarily depends on ankle stiffness during human hopping.
When humans hop in place or run forward, they adjust leg stiffness to accommodate changes in stride frequency or surface stiffness. The goal of the present study was to determine the mechanisms by which humans adjust leg stiffness during hopping in place. Five subjects hopped in place at 2.2 Hz while we collected force platform and kinematic data. Each subject completed trials in which they hopped to whatever height they chose ("preferred height hopping") and trials in which they hopped as high as possible ("maximum height hopping"). Leg stiffness was approximately twice as great for maximum height hopping as for preferred height hopping. Ankle torsional stiffness was 1.9-times greater while knee torsional stiffness was 1.7-times greater in maximum height hopping than in preferred height hopping. We used a computer simulation to examine the sensitivity of leg stiffness to the observed changes in ankle and knee stiffness. Our model consisted of four segments (foot, shank, thigh, head-arms-trunk) interconnected by three torsional springs (ankle, knee, hip). In the model, increasing ankle stiffness by 1.9-fold, as observed in the subjects, caused leg stiffness to increase by 2.0-fold. Increasing knee stiffness by 1.7-fold had virtually no effect on leg stiffness. Thus, we conclude that the primary mechanism for leg stiffness adjustment is the adjustment of ankle stiffness.
Adult↗
Beer spoilage bacteria and hop resistance.
For brewing industry, beer spoilage bacteria have been problematic for centuries. They include some lactic acid bacteria such as Lactobacillus brevis, Lactobacillus lindneri and Pediococcus damnosus, and some Gram-negative bacteria such as Pectinatus cerevisiiphilus, Pectinatus frisingensis and Megasphaera cerevisiae. They can spoil beer by turbidity, acidity and the production of unfavorable smell such as diacetyl or hydrogen sulfide. For the microbiological control, many advanced biotechnological techniques such as immunoassay and polymerase chain reaction (PCR) have been applied in place of the conventional and time-consuming method of incubation on culture media. Subsequently, a method is needed to determine whether the detected bacterium is capable of growing in beer or not. In lactic acid bacteria, hop resistance is crucial for their ability to grow in beer. Hop compounds, mainly iso-alpha-acids in beer, have antibacterial activity against Gram-positive bacteria. They act as ionophores which dissipate the pH gradient across the cytoplasmic membrane and reduce the proton motive force (pmf). Consequently, the pmf-dependent nutrient uptake is hampered, resulting in cell death. The hop-resistance mechanisms in lactic acid bacteria have been investigated. HorA was found to excrete hop compounds in an ATP-dependent manner from the cell membrane to outer medium. Additionally, increased proton pumping by the membrane bound H(+)-ATPase contributes to hop resistance. To energize such ATP-dependent transporters hop-resistant cells contain larger ATP pools than hop-sensitive cells. Furthermore, a pmf-dependent hop transporter was recently presented. Understanding the hop-resistance mechanisms has enabled the development of rapid methods to discriminate beer spoilage strains from nonspoilers. The horA-PCR method has been applied for bacterial control in breweries. Also, a discrimination method was developed based on ATP pool measurement in lactobacillus cells. However, some potential hop-resistant strains cannot grow in beer unless they have first been exposed to subinhibitory concentration of hop compounds. The beer spoilage ability of Pectinatus spp. and M. cerevisiae has been poorly studied. Since all the strains have been reported to be capable of beer spoiling, species identification is sufficient for the breweries. However, with the current trend of beer flavor (lower alcohol and bitterness), there is the potential risk that not yet reported bacteria will contribute to beer spoilage. Investigation of the beer spoilage ability of especially Gram-negative bacteria may be useful to reduce this risk.
ATP-Binding Cassette Transporters↗
Analysis of the structure and function of the transcriptional coregulator HOP.
Homeodomain-only protein (HOP) is an 8-kDa transcriptional corepressor that is essential for the normal development of the mammalian heart. Previous studies have shown that HOP, which consists entirely of a putative homeodomain, acts downstream of Nkx2.5 and associates with the serum response factor (SRF), repressing transcription from SRF-responsive genes. HOP is also able to recruit histone deacetylase (HDAC) activity, consistent with its ability to repress transcription. Unlike other classic homeodomain proteins, HOP does not appear to interact with DNA, although it has been unclear if this is because of an overall divergent structure or because of specific amino acid differences between HOP and other homeodomains. To work toward an understanding of HOP function, we have determined the 3D structure of full-length HOP and used a range of biochemical assays to define the parts of the protein that are functionally important for its repression activity. We show that HOP forms a classical homeodomain fold but that it cannot recognize double stranded DNA, a result that emphasizes the importance of caution in predicting protein function from sequence homology alone. We also demonstrate that two distinct regions on the surface of HOP are required for its ability to repress an SRF-driven reporter gene, and it is likely that these motifs direct interactions between HOP and partner proteins such as SRF- and HDAC-containing complexes. Our results demonstrate that the homeodomain fold has been co-opted during evolution for functions other than sequence-specific DNA binding and suggest that HOP functions as an adaptor protein to mediate transcriptional repression.
Amino Acid Motifs↗
Hop cleavage and function in granzyme B-induced apoptosis.
Granzyme B (GzmB) is a cytotoxic protease found in the granules of natural killer cells and cytotoxic T lymphocytes. GzmB cleaves multiple intracellular protein substrates, leading to caspase activation, DNA fragmentation, cytoskeletal instability, and rapid induction of target cell apoptosis. However, no known individual substrate is required for GzmB to induce apoptosis. GzmB is therefore thought to initiate multiple cell death pathways simultaneously to ensure the death of target cells. We previously identified Hop (Hsp70/Hsp90-organizing protein) as a GzmB substrate in a proteomic survey (Bredemeyer, A. J., Lewis, R. M., Malone, J. P., Davis, A. E., Gross, J., Townsend, R. R., and Ley, T. J. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 11785-11790). Hop is a co-chaperone for Hsp70 and Hsp90, which have been implicated in the negative regulation of apoptosis. We therefore hypothesized that Hop may have an anti-apoptotic function that is abolished upon cleavage, lowering the threshold for GzmB-induced apoptosis. Here, we show that Hop was cleaved directly by GzmB in vitro and in cells undergoing GzmB-induced apoptosis. Expression of the two cleavage fragments of Hop did not induce cell death. Although cleavage of Hop by GzmB destroyed Hop function in vitro, both cells overexpressing GzmB-resistant Hop and cells with a 90-95% reduction in Hop levels exhibited unaltered susceptibility to GzmB-induced death. We conclude that Hop per se does not set the threshold for susceptibility to GzmB-induced apoptosis. Although it is possible that Hop may be cleaved by GzmB as an "innocent bystander" during the induction of apoptosis, it may also act to facilitate apoptosis in concert with other GzmB substrates.
Animals↗
Clinical and immunologic changes after allergen immunotherapy with Hop Japanese pollen.
BACKGROUND AND OBJECTIVE: Hop Japanese (Hop J) pollen has been reported as one of the major causative pollen allergens in the autumn season. There have been no published data regarding the clinical and immunologic effects of Hop J pollen immunotherapy in sensitized patients. In this study, we evaluated clinical and immunologic effects of Hop J immunotherapy. PATIENTS AND METHODS: Pollens were collected in our area, and "Depo-Hop J" was prepared in the laboratory of Allergopharma (Reinbek, Germany). Fifteen asthmatic patients who had Hop J immunotherapy for > 1 year were enrolled. Their clinical parameters, such as asthma symptom scores, were monitored. Skin reactivity to Hop J and degree of airway hyperresponsiveness to methacholine were measured before and 1 year after the immunotherapy. Sera were collected before the immunotherapy, at the end of initial therapy, and 1 year after the therapy. Serum total IgE levels were compared by radioimmunoassay. Serum-specific IgE, IgG1, and IgG4 levels to Hop J were compared by ELISA. To evaluate the changes of cellular mechanisms, soluble CD30 (sCD30), soluble interleukin (IL)-2 receptor (sIL-2R), soluble CD23 (sCD23), and IL-10 levels were measured by ELISA. RESULTS: Specific IgG1 and IgG4 levels began to increase at the end of the initial therapy (P < 0.05) with significant decreases in symptom scores (P < 0.05), whereas total and specific IgE levels showed variable responses during the immunotherapy with no statistical significance (P > 0.05). Serum sIL-2R and sCD30 levels decreased significantly (P < 0.05) 1 year after immunotherapy. No significant changes were noted in sCD23, IL-10, skin reactivity to Hop J, or airway responsiveness to methacholine (P > 0.05). CONCLUSIONS: We are certain that Hop J allergen immunotherapy, if carried out properly according to suitable indications, can favorably influence asthma. Thus, an increase in specific IgG4 and IgG1 antibodies and reduction of a possible Th2 lymphocyte marker (sCD30) may be associated with symptomatic improvements.
Adolescent↗