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Modulation of short latency stretch reflexes during human hopping.

To gain insight into central and peripheral reflex control mechanisms in moving humans we have investigated short latency stretch reflex activity in m. triceps surae during two legged hopping. The objectives were: (1) to compare movement induced short latency stretch reflexes in soleus and medial gastrocnemius (MG) muscles, (2) to determine the relationship between the size of these reflexes and the muscle spindle stretch velocities, and (3) to compare the size of the movement induced short latency stretch reflexes and the H-reflexes simultaneously. Six well-trained healthy male subjects participated and they hopped at three different work rates. Surface electromyogram (EMG) and H-reflexes were recorded during hopping. Muscle spindle length changes were estimated as the difference between estimated origin-to-insertion length changes and tendon length changes. The important findings were that during hopping: (1) movement induced short latency stretch reflexes were observed consistently in soleus, (2) the EMG amplitude of this stretch reflex was negatively correlated with the estimated peak muscle spindle stretch velocity (rs = -0.52, P < 0.02), and (3) the amplitude of the soleus H-reflex at touchdown did not change in parallel with the stretch reflex. The negative correlation observed between the stretch reflex and the estimated peak muscle spindle stretch velocity in soleus is opposite to the basic velocity sensitive behaviour of stretch reflexes mechanically elicited during resting conditions. Possible control mechanisms are discussed. Additionally, muscle spindle length changes estimated from changes in the skeletal movements (joint angles) should be inferred cautiously because of tendon compliance, especially at high tendon forces.

Adult↗

Modal decomposition of hopping states in cellular flames.

We use Karhunen-Loeve (KL) decomposition of video images from an experiment to analyze a spatiotemporal dynamic state, unique to cellular flames, referred to as a "hopping state." Ordered states of cellular flames on a circular burner consist of one or two concentric rings of luminous cells. The hopping states correspond to the motions of individual cells in a ring sequentially executing abrupt changes in their angular position, while the other cells in the ring remain symmetric and at rest. KL decomposition separates the spatial and temporal characteristics of the hopping motion. The underlying symmetries of the experiment allow us to deduce a set of normal form equations that describe the formation of these states. We find that they result from secondary bifurcations connecting two primary branches of traveling waves. The solutions corresponding to hopping states exist as mixed-mode solutions away from the secondary bifurcations. (c) 1999 American Institute of Physics.

Journal Article↗

Calculating the hopping times of confined fluids: two hard disks in a box.

The dynamical transition between the anomalous single file diffusion of highly confined fluids and bulk normal diffusion can be described by a phenomenological model involving a particle hopping time tau(hop). We suggest a theoretical formalism that will be useful for the calculation of tau(hop) for a variety of systems and test it using a simple model consisting of two hard disks confined to a rectangular box with hard walls. In the case where the particles are moving diffusively, we find the hopping time diverges as a power law in the threshold region with an exponent of -(3/2). Under conditions where the particles move inertially, transition state theory predicts a power law behavior with an exponent of -2. Molecular dynamics simulations confirm the transition state theory result for inertial dynamics, while Brownian dynamics simulations suggest the scaling exponent is highly sensitive to the details of the algorithm.

Journal Article↗

Long-range charge hopping in DNA.

The fundamental mechanisms of charge migration in DNA are pertinent for current developments in molecular electronics and electrochemistry-based chip technology. The energetic control of hole (positive ion) multistep hopping transport in DNA proceeds via the guanine, the nucleobase with the lowest oxidation potential. Chemical yield data for the relative reactivity of the guanine cations and of charge trapping by a triple guanine unit in one of the strands quantify the hopping, trapping, and chemical kinetic parameters. The hole-hopping rate for superexchange-mediated interactions via two intervening AT base pairs is estimated to be 10(9) s(-1) at 300 K. We infer that the maximal distance for hole hopping in the duplex with the guanine separated by a single AT base pair is 300 +/- 70 A. Although we encounter constraints for hole transport in DNA emerging from the number of the mediating AT base pairs, electron transport is expected to be nearly sequence independent because of the similarity of the reduction potentials of the thymine and of the cytosine.

Journal Article↗

Bacterial lipopolysaccharide induces expression of the stress response genes hop and H411.

CD14-transfected Chinese hamster ovary K1 fibroblasts (CHO/CD14) respond to lipopolysaccharide (LPS) by metabolizing arachidonic acid and with translocation of NF-kappaB to the nucleus. Although previous experiments failed to identify the production of tumor necrosis factor-alpha and interleukin (IL)-1beta by CHO/CD14 cells, LPS did induce the expression of IL-6 mRNA and the subsequent release of the IL-6 protein. To identify additional LPS-inducible genes, a cDNA library derived from LPS-stimulated CHO/CD14 cells was screened by subtractive hybridization. Fourteen genes were found to be expressed differentially, and two were analyzed in detail: hop (Hsp70/Hsp90-organizing protein), which is the hamster homologue of the stress-inducible yeast gene, STI1, and clone H411, which encodes a novel LPS-inducible growth factor. In response to LPS, the expression of Hop mRNA was also increased in both the murine macrophage cell line, RAW 264.7, as well as in primary hamster macrophages. This suggested that the up-regulation of Hop expression is part of the macrophage stress response to LPS. Clone H411 encodes a protein in the epidermal growth factor-like repeat protein family. Overexpression of H411 cDNA in the RAW 264.7 macrophage cell line promoted an increased growth rate, suggesting that expression of H411 is part of the proliferative cell response to LPS. Both Hop and H411 represent novel gene products not previously recognized as part of the complex biological response to endotoxin.

Amino Acid Sequence↗

The common tetratricopeptide repeat acceptor site for steroid receptor-associated immunophilins and hop is located in the dimerization domain of Hsp90.

Structurally related tetratricopeptide repeat motifs in steroid receptor-associated immunophilins and the STI1 homolog, Hop, mediate the interaction with a common cellular target, hsp90. We have identified the binding domain in hsp90 for cyclophilin 40 (CyP40) using a two-hybrid system screen of a mouse cDNA library. All isolated clones encoded the intact carboxyl terminus of hsp90 and overlapped with a common region corresponding to amino acids 558-724 of murine hsp84. The interaction was confirmed in vitro with bacterially expressed CyP40 and deletion mutants of hsp90beta and was delineated further to a 124-residue COOH-terminal segment of hsp90. Deletion of the conserved MEEVD sequence at the extreme carboxyl terminus of hsp90 precludes interaction with CyP40, signifying an important role for this motif in hsp90 function. We show that CyP40 and Hop display similar interaction profiles with hsp90 truncation mutants and present evidence for the direct competition of Hop and FK506-binding protein 52 with CyP40 for binding to the hsp90 COOH-terminal region. Our results are consistent with a common tetratricopeptide repeat interaction site for Hop and steroid receptor-associated immunophilins within a discrete COOH-terminal domain of hsp90. This region of hsp90 mediates ATP-independent chaperone activity, overlaps the hsp90 dimerization domain, and includes structural elements important for steroid receptor interaction.

Amino Acid Sequence↗

In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus.

1. Several unique flavonoid compounds have recently been isolated from hops, Humulus lupulus, and their presence has been detected in beer. Their chemical structures are similar to other plant-derived compounds, many present in the human diet, that have been shown to have cancer chemopreventive properties due, in part, to inhibition of cytochrome P450 enzymes that activate carcinogens. Additionally, preliminary studies have shown these flavonoids (at 100 microM) to be inhibitory of P450-mediated activation reactions in a variety of in vitro systems. Thus, the in vitro effects of these phytochemicals on cDNA-expressed human CYP1A1, CYP1B1, CYP1A2, CYP3A4 and CYP2E1 were currently examined by the use of diagnostic substrates and the carcinogen AFB1. 2. At 10 microM, the prenylated chalcone, xanthohumol (XN), almost completely inhibited the 7-ethoxyresorufin O-deethylase (EROD) activity of CYP1A1. At the same concentration, other hop flavonoids decreased the EROD activity by 90.8-27.0%. 3. At 10 microM, XN completely eliminated CYP1B1 EROD activity, whereas the other hop flavonoids showed varying degrees of inhibitory action ranging from 99.3 to 1.8%. 4. In contrast, the most effective inhibitors of CYP1A2 acetanilide 4-hydroxylase activity were the two prenylated flavonoids, 8-prenylnaringenin (8PN) and isoxanthohumol (IX), which produced > 90% inhibition when added at concentrations of 10 microM. 5. CYP1A2 metabolism of the carcinogen AFB1 was also inhibited by IX and 8PN as shown by decreased appearance of dihydrodiols and AFM1 as analysed by hplc. IX and 8PN also decreased covalent binding of radiolabelled AFB1 to microsomal protein in a concomitant manner. 6. XN, IX and 8PN, however, were poor inhibitors of CYP2E1 and CYP3A4 as measured by their effect on chorzoxazone hydroxylase and nifedipine oxidase activities respectively. 7. These results suggest that the hop flavonoids are potent and selective inhibitors of human cytochrome P450 and warrant further in vivo investigations.

Aflatoxin B1↗

Loss of spr-5 bypasses the requirement for the C.elegans presenilin sel-12 by derepressing hop-1.

Presenilins are part of a protease complex that is responsible for the intramembraneous cleavage of the amyloid precursor protein involved in Alzheimer's disease and of Notch receptors. In Caenorhabditis elegans, mutations in the presenilin sel-12 result in a highly penetrant egg-laying defect. spr-5 was identified as an extragenic suppressor of the sel-12 mutant phenotype. The SPR-5 protein has similarity to the human polyamine oxidase-like protein encoded by KIAA0601 that is part of the HDAC-CoREST co-repressor complex. Suppression of sel-12 by spr-5 requires the activity of HOP-1, the second somatic presenilin in C.elegans. spr-5 mutants derepress hop-1 expression 20- to 30-fold in the early larval stages when hop-1 normally is almost undetectable. SPR-1, a C.elegans homologue of CoREST, physically interacts with SPR-5. Moreover, down-regulation of SPR-1 by mutation or RNA interference also bypasses the need for sel-12. These data strongly suggest that SPR-5 and SPR-1 are part of a CoREST-like co-repressor complex in C.elegans. This complex might be recruited to the hop-1 locus controlling its expression during development.

Amino Acid Sequence↗

Leg power and hopping stiffness: relationship with sprint running performance.

PURPOSE: Although sprint performance undoubtedly involves muscle power, the stiffness of the leg also determines sprint performance while running at maximal velocity. Results that include both of these characteristics have not been directly obtained in previous studies on human runners. We have therefore studied the link between leg power, leg stiffness, and sprint performance. METHODS: The acceleration and maximal running velocity developed by 11 subjects (age 16 +/- 1) during a 40-m sprint were measured by radar. Their leg muscle volumes were estimated anthropometrically. Leg power was measured by an ergometric treadmill test and by a hopping test. Each subject executed a maximal sprint acceleration on the treadmill equipped with force and speed transducers, from which forward power was calculated. A hopping jump test was executed at 2 Hz on a force platform. Leg stiffness was calculated using the flight and contact times of the hopping test. RESULTS: The treadmill forward leg power was correlated with both the initial acceleration (r = 0.80, P < 0.01) and the maximal running velocity (r = 0.73, P < 0.05) during track sprinting. The leg stiffness calculated from hopping was significantly correlated with the maximal velocity but not with acceleration. CONCLUSION: Although muscle power is needed for acceleration and maintaining a maximal velocity in sprint performance, high leg stiffness may be needed for high running speed. The ability to produce a stiff rebound during the maximal running velocity could be explored by measuring the stiffness of a rebound during a vertical jump.

Adolescent↗

Hop stunt viroid strains from dapple fruit disease of plum and peach in Japan.

Viroids have been isolated from plum trees (Prunus salicina Lindley) affected with plum dapple fruit disease and from peach trees (Prunus persica Batsch) showing dapple fruit symptoms. The viroids were inoculated mechanically to cucurbitaceous plants, in which symptoms typical of hop stunt viroid (HSV) infection appeared. The complete nucleotide sequences of an isolate from plum and an isolate from peach (AF isolate) were shown to be identical, consisting of 297 nucleotides with a 93.6% sequence homology to HSV-hop. Another isolate from peach (A9 isolate) also consists of 297 nucleotides, but the sequence homology to HSV-hop is 99.7%, showing only one nucleotide replacement. These results indicate that these three viroids are strains of HSV, which we designate HSV-plum, HSV-peach (AF) and HSV-peach (A9), respectively. Comparative analysis of the nucleotide sequences of HSV strains from hop, grapevine, citrus, cucumber, plum and peach revealed variable and conserved regions in the HSV molecule. In Japan, these viroids are closely related not only to dapple fruit disease in plum cv. Taiyo, but also to dapple fruit symptoms on peach cv. Asama-Hakutou.

Base Sequence↗

Universality class of the restricted solid-on-solid model with hopping.

We study the restricted solid-on-solid (RSOS) model with finite hopping distance l(0), using both analytical and numerical methods. Analytically, we use the hard-core bosonic field theory developed by the authors [Phys. Rev. E 62, 7642 (2000)] and derive the Villain-Lai-Das Sarma (VLD) equation for the l(0)=infinity case, which corresponds to the conserved RSOS (CRSOS) model and the Kardar-Parisi-Zhang (KPZ) equation for all finite values of l(0). Consequently, we find that the CRSOS model belongs to the VLD universality class and that the RSOS models with any finite hopping distance belong to the KPZ universality class. There is no phase transition at a certain finite hopping distance contrary to the previous result. We confirm the analytic results using the Monte Carlo simulations for several values of the finite hopping distance.

Journal Article↗

horC confers beer-spoilage ability on hop-sensitive Lactobacillus brevis ABBC45cc.

AIMS: To determine whether horC confers beer-spoilage ability and to evaluate the validity of horC as a trans-species genetic marker for differentiating the beer-spoilage ability of lactic acid bacteria (LAB). METHODS AND RESULTS: Hop-sensitive Lactobacillus brevis ABBC45cc was transformed with an expression plasmid, pHYchorBC, containing putative multidrug resistance gene horC and its putative regulator horB, and the transformant was designated as ABBC45cc/pHYchorBC. As a control, ABBC45cc was transformed with pHYchorB that contains horB, and the transformed strain was designated as ABBC45cc/pHYchorB. As a result of beer-spoilage assay of these transformants, ABBC45cc/pHYchorBC exhibited beer-spoilage ability, whereas ABBC45cc/pHYchorB did not. Furthermore ABBC45cc/pHYchorBC showed higher hop resistance than ABBC45cc/pHYchorB, accounting for the differences in beer-spoilage ability observed between the two transformants. ABBC45cc/pHYchorBC also exhibited higher resistance to various structurally unrelated drugs, compared with ABBC45cc/pHYchorB. CONCLUSIONS: horC was shown to confer hop resistance and beer-spoilage ability on ABBC45cc by presumably encoding a multidrug transporter. SIGNIFICANCE AND IMPACT OF THE STUDY: The finding that horC plays an important role in hop resistance and beer-spoilage ability supports the validity of horC as a trans-species genetic marker for differentiating the beer-spoilage ability of LAB.

Bacterial Proteins↗

Clinical evaluation of the heterologous oocyte penetration (HOP) test.

The heterologous oocyte penetration (HOP) test, using zona-free hamster oocytes, was used to assess the fertilising capacity of human spermatozoa. There was good correlation between the ability of ejaculated spermatozoa to penetrate the zona-free hamster oocytes and intact human oocytes. Using epididymal spermatozoa, the HOP test results showed that the ability to penetrate oocytes was acquired during their passage through the epididymis. Applied clinically, the HOP test enables a group of infertile men to be identified with a functional defect of their spermatozoa; these men may not be identified at routine seminal fluid analysis. Men with two negative HOP test results were confirmed as being infertile since their wives, if normal, conceived rapidly when donor spermatozoa were artificially inseminated.

Animals↗

Insights into glandular trichome biology from analysis of organ-specific gene expression programmes in cannabis, hop and tomato.

Glandular trichomes (GTs) are epidermal outgrowths in which diverse specialised (secondary) metabolites are synthesised and stored. Cannabis (Cannabis sativa L.) and its close relative hop (Humulus lupulus L.) have pharmaceutical and industrial significance due to the presence of these metabolites in their GTs. We examined the conservation or divergence of the specific transcriptional programmes underlying GT biology. To achieve this, we generated transcriptome atlases of trichomes, flower, leaf, stem and root for cannabis, hop and tomato. We found that 12.9, 10.1 and 16.8% of cannabis, hop and tomato genes, respectively, were expressed organ/tissue specifically across all organs/tissues. Transcription factors (TFs) on average accounted for 7.5% of the organ-specific transcriptome and likely regulate organ-specific functions. We also conducted weighted gene co-expression network analysis and gene regulatory network (GRN) analysis to identify key regulators of GT function across the species and validated our predictions by DNA affinity purification sequencing for a subset of the cannabis and tomato GT TFs. The GRNs specific to cannabis or hop GTs were enriched for TFs and target genes associated with specialised metabolism, reflecting their species-specific nature. Conversely, the shared GRN components (identified via orthology analysis) were involved in highly conserved processes, such as flavonoid biosynthesis, solute transport and metabolite storage. Together, these GRNs and the associated transcriptome atlases are valuable resources to improve our knowledge of GT function and organ-specific genome regulation.

Solanum lycopersicum↗

Observations on the control of stepping and hopping movements in man.

1. The presence of a form of stretch reflex, previously described in the arm by other authors, has been confirmed in the gastrocnemius muscle of the human leg. The electromyographic (e.m.g.) manifestation of this reflex occurred 120 msec (S.E. of mean = 3.5 msec) following a sharply applied, and maintained, dorsiflexing force to the foot. This form of response is referred to in this article as the Functional Stretch Reflex (FSR).2. To determine the contribution of the FSR to the control of normal leg movement, the e.m.g. activity in the above muscle was monitored during single downward steps of 12.7, 25.4 and 38.1 cm and during repetitive, rhythmic, hopping movements on one foot.3. It was found that e.m.g. activity associated with steps to the ground began 141 msec (S.E. of mean = 8.5 msec) before contact with the ground and ended 131 msec (S.E. of mean = 7.6 msec) after contact, when the e.m.g. usually became temporarily inactive.4. It is inferred from these results that the muscular deceleration associated with landing was brought about by the release of a pre-programmed pattern of neuromuscular activity which was inaccessible to reflex activity resulting from the mechanical event of landing, rather than by a stretch reflex.5. It was found that subjects chose their preferred frequency of hopping with great accuracy and consistency. The mean value obtained was 2.06 Hz (S.E. of mean = 0.02 Hz).6. At the preferred frequency, e.m.g. activity began 84 msec (S.E. of mean = 9.6 msec) before and terminated 263 msec (S.E. of mean = 10 msec) after contact with the ground.7. It is inferred that in rhythmical hopping and perhaps also in running, each landing is effected, as in single steps, by a predetermined pattern of neuromuscular activity. However, when hopping at the preferred frequency, the take-off phase of muscular activity is timed to make maximal use of the FSR, i.e. between 120 and 260 msec after initial contact.8. The results emphasize the importance of pre-programming complex muscular contractions suitable for opposing sudden passive stretching forces, and of initiating them prior to the onset of these forces.

Adult↗

Identification of human hepatic cytochrome P450 enzymes involved in the metabolism of 8-prenylnaringenin and isoxanthohumol from hops (Humulus lupulus L.).

The female flowers of hops (Humulus lupulus L.) are used in the brewing of beer and are under investigation for use in dietary supplements for the management of menopausal symptoms in women. Hop extracts contain the weakly estrogenic compound isoxanthohumol (IX), proestrogenic xanthohumol, and the potent estrogen 8-prenylnaringenin (8PN). Because IX can be metabolized in the human liver to form 8PN, the specific cytochrome P450 (P450) enzymes responsible for this O-demethylation reaction were identified. In addition, the enzymes that convert IX and 8PN to their most abundant metabolites were identified because these metabolic pathways might also affect the estrogenicity of hop preparations. Specifically, the P450 enzymes that catalyze the oxidation of the prenyl side chains of IX and 8PN into trans- or cis-alcohols were investigated. Human liver microsomes and monoclonal antibodies that inhibit specific P450 enzymes were used in combination with liquid chromatography/mass spectrometry to identify the enzymes responsible for these transformations. CYP2C19 was found to catalyze the formation of both cis- and trans-alcohols of the prenyl side chain of 8PN with K(m) values of 14.8 +/- 3.2 and 16.6 +/- 4.6 microM, respectively. CYP2C8 converted 8PN regioselectively to the trans-alcohol of the prenyl group with a K(m) of 3.7 +/- 0.9 microM. Finally, CYP1A2 was found to catalyze the O-demethylation of IX to generate 8PN, with a K(m) value of 17.8 +/- 3.7 microM. These results suggest that the estrogenicity of hop constituents in vivo will depend in part on metabolic conversion that may show individual variation.

Antibodies, Monoclonal↗

Lateral hopping of molecules induced by excitation of internal vibration mode.

We demonstrate electron-stimulated migration for carbon monoxide (CO) molecules adsorbed on the Pd(110) surface, which is initiated by the excitation of a high-frequency (HF) vibrational mode (C-O stretching mode) with inelastic tunneling electrons from the tip of scanning tunneling microscopy. The hopping phenomenon, however, cannot be detected for CO/Cu(110), even though the hopping barrier is lower than in the CO/Pd(110) case. A theoretical model, which is based on the anharmonic coupling between low-frequency modes (the hindered-translational mode related to the lateral hopping) and the HF mode combined with electron-hole pair excitation, can explain why the hopping of CO is observed on Pd(110) but not on Cu(110).

Journal Article↗

Hop resistance in the beer spoilage bacterium Lactobacillus brevis is mediated by the ATP-binding cassette multidrug transporter HorA.

Lactobacillus brevis is a major contaminant of spoiled beer. The organism can grow in beer in spite of the presence of antibacterial hop compounds that give the beer a bitter taste. The hop resistance in L. brevis is, at least in part, dependent on the expression of the horA gene. The deduced amino acid sequence of HorA is 53% identical to that of LmrA, an ATP-binding cassette multidrug transporter in Lactococcus lactis. To study the role of HorA in hop resistance, HorA was functionally expressed in L. lactis as a hexa-histidine-tagged protein using the nisin-controlled gene expression system. HorA expression increased the resistance of L. lactis to hop compounds and cytotoxic drugs. Drug transport studies with L. lactis cells and membrane vesicles and with proteoliposomes containing purified HorA protein identified HorA as a new member of the ABC family of multidrug transporters.

ATP-Binding Cassette Transporters↗