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A better understanding of the strains experienced by the Achilles tendon during commonly prescribed exercises and locomotor tasks is needed to improve efficacy of Achilles tendon training and rehabilitation programs. The aim of this study was to estimate in vivo free Achilles tendon strain during selected rehabilitation, locomotor, jumping, and landing tasks. Sixteen trained runners with no symptoms of Achilles tendinopathy participated in this study. Personalized free Achilles tendon moment arm and force-strain curve were obtained from imaging data and used in conjunction with motion capture and surface electromyography to estimate free Achilles tendon strain using electromyogram-informed neuromusculoskeletal modeling. There was a strong correspondence between Achilles tendon force estimates from the present study and experimental data reported in the literature (

The deep hip muscles are often omitted in studies investigating hip contact forces using neuromusculoskeletal modelling methods. However, recent evidence indicates the deep hip muscles have potential to change the direction of hip contact force and could have relevance for hip contact loading estimates. Further, it is not known whether deep hip muscle excitation patterns can be accurately estimated using neuromusculoskeletal modelling or require measurement (through invasive and time-consuming methods) to inform models used to estimate hip contact forces. We calculated hip contact forces during walking, squatting, and squat-jumping for 17 participants using electromyography (EMG)-informed neuromusculoskeletal modelling with (informed) and without (synthesized) intramuscular EMG for the deep hip muscles (piriformis, obturator internus, quadratus femoris). Hip contact force magnitude and direction, calculated as the angle between hip contact force and vector from femoral head to acetabular center, were compared between configurations using a paired t-test deployed through statistical parametric mapping (P 0.05). Additionally, root mean square error, correlation coefficients (R

A better understanding of deep hip muscle function is needed to establish whether retraining and strengthening these muscles is a worthwhile target for rehabilitation. This study aimed to determine the contribution of the deep hip muscles to the direction of hip loading in the acetabulum. Hip contact forces were calculated during walking and squatting for 12 participants (age: 24 ± 4 yrs, 4 females) using electromyography-informed neuromusculoskeletal modelling. Models were configured with different deep hip muscle activation levels: deep hip muscles (piriformis, obturator internus and externus, gemellus superior and inferior, and quadratus femoris) informed by intramuscular electromyography measurements (i.e., normal activation; assisted activation) and simulated with zero (no activation) or maximal (maximal activation) activation. The angle between the hip contact force and the vector from the femoral head to the acetabular center (hip contact force angle) was calculated for all configurations, where lower angles equated to hip loading directed towards the acetabular center. The position and spread of acetabular loading during both tasks were calculated for all configurations and compared using a within-participant analysis of variance via statistical parametric mapping (P 0.05). Maximal activation resulted in lower hip contact force angles and more anterior-inferior oriented, albeit a slightly reduced, spread of acetabular loading compared to assisted activation and no activation. Results suggest that, if activated maximally, the deep hip muscles can change the direction of hip loading away from commonly damaged areas of acetabular cartilage. Targeted training of these muscles may be relevant for individuals with hip pathology who present with unfavorable regional loading and/or cartilage lesions.

Three-dimensional gait analysis, employing rigid-body motion analysis models, is commonly used for clinical decision-making, treatment, and outcome assessment in children with neuromusculoskeletal disorders, e.g. cerebral palsy. Most multi-segment rigid body models employed in biomechanics use a simplified knee hinge joint that is poorly representative of the complex tibiofemoral joint (TFJ) motion, which must compromise clinical decision-making. More complex TFJ models featuring rigid-spherical articular contacts and ligamentous constraints, with subject-specific and/or generic geometrical parameters, can estimate 6 degree-of-freedom TFJ kinematics during gait in adults [2]. However, no studies have assessed TFJ and ligament kinematics during gait using a rigid-body lower limb model incorporating a fully subject-specific paediatric kinematic knee model with articular contacts and minimally deformable ligaments. This was therefore the aim of the current study.

Cartilage T2 relaxation time in isolated anterior cruciate ligament reconstruction (ACLR) without concomitant meniscal pathology and their changes over time remain unclear. The purpose of this exploratory study was to: (i) compare cartilage T2 relaxation time (T2 values) in people with isolated ACLR at 2-3 years post-surgery (baseline) and matched healthy controls and; (ii) evaluate the subsequent 2-year change in T2 values in people with ACLR. Twenty-eight participants with isolated ACLR and nine healthy volunteers underwent knee magnetic resonance imaging (MRI) at baseline; 16 ACLR participants were re-imaged 2 years later. Cartilage T2 values in full thickness, superficial layers, and deep layers were quantified in the tibia, femur, trochlear, and patella. Between-group comparisons at baseline were performed using analysis of covariance adjusting for age, sex, and body mass index. Changes over time in the ACLR group were evaluated using paired sample t-tests. ACLR participants showed significantly higher (p = 0.03) T2 values in the deep layer of medial femoral condyle at baseline compared to controls (mean difference 4.4 ms [13%], 95%CI 0.4, 8.3 ms). Over 2 years, ACLR participants showed a significant reduction (p = 0.04) in T2 value in the deep layer of lateral tibia (mean change 1.4 ms [-7%], 95%CI 0.04, 2.8 ms). The decrease in T2 values suggests improvement in cartilage composition in the lateral tibia (deep layer) of ACLR participants. Further research with larger ACLR cohorts divided according to meniscal status and matched healthy cohorts are needed to further understand cartilage changes post-ACLR. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2022-2029, 2018.

Background: Prevention of knee osteoarthritis (OA) following anterior cruciate ligament (ACL) rupture and reconstruction is vital. Risk of postreconstruction knee OA is markedly increased by concurrent meniscal injury. It is unclear whether reconstruction results in normal relationships between tibiofemoral contact forces and cartilage morphology and whether meniscal injury modulates these relationships. Hypotheses: Since patients with isolated reconstructions (ie, without meniscal injury) are at lower risk for knee OA, we predicted that relationships between tibiofemoral contact forces and cartilage morphology would be similar to those of normal, healthy knees 2 to 3 years postreconstruction. In knees with meniscal injuries, these relationships would be similar to those reported in patients with knee OA, reflecting early degenerative changes. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Three groups were examined: (1) 62 patients who received single-bundle hamstring reconstruction with an intact, uninjured meniscus (mean age, 29.8 ± 6.4 years; mean weight, 74.9 ± 13.3 kg); (2) 38 patients with similar reconstruction with additional meniscal injury (ie, tear, repair) or partial resection (mean age, 30.6 ± 6.6 years; mean weight, 83.3 ± 14.3 kg); and (3) 30 ligament-normal, healthy individuals (mean age, 28.3 ± 5.2 years; mean weight, 74.9 ± 14.9 kg) serving as controls. All patients underwent magnetic resonance imaging to measure the medial and lateral tibial articular cartilage morphology (volumes and thicknesses). An electromyography-driven neuromusculoskeletal model determined medial and lateral tibiofemoral contact forces during walking. General linear models were used to assess relationships between tibiofemoral contact forces and cartilage morphology. Results: In control knees, cartilage was thicker compared with that of isolated and meniscal-injured ACL-reconstructed knees, while greater contact forces were related to both greater tibial cartilage volumes (medial: R 2 = 0.43, β = 0.62, P = .000; lateral: R 2 = 0.19, β = 0.46, P = .03) and medial thicknesses (R 2 = 0.24, β = 0.48, P = .01). In the overall group of ACL-reconstructed knees, greater contact forces were related to greater lateral cartilage volumes (R 2 = 0.08, β = 0.28, P = .01). In ACL-reconstructed knees with lateral meniscal injury, greater lateral contact forces were related to greater lateral cartilage volumes (R 2 = 0.41, β = 0.64, P = .001) and thicknesses (R 2 = 0.20, β = 0.46, P = .04). Conclusion: At 2 to 3 years postsurgery, ACL-reconstructed knees had thinner cartilage compared with healthy knees, and there were no positive relationships between medial contact forces and cartilage morphology. In lateral meniscal-injured reconstructed knees, greater contact forces were related to greater lateral cartilage volumes and thicknesses, although it was unclear whether this was an adaptive response or associated with degeneration. Future clinical studies may seek to establish whether cartilage morphology can be modified through rehabilitation programs targeting contact forces directly in addition to the current rehabilitation foci of restoring passive and dynamic knee range of motion, knee strength, and functional performance.

This paper describes the beginnings of a futures scenario development and implementation process which forms a key aspect of the community work of Transition Adelaide Hills (TAH). While TAH is registered as a full member of the Transition Towns movement, TAH is, like all groups, developing along lines that suit the unique environment and talents of its members. The story starts with a brief history, including the context of the study, and then describes how TAH has gone about developing a first draft of a futures scenario to guide its decision making. Refereed/Peer-reviewed

Joint kinematics can be calculated by Direct Kinematics (DK), which is used in most clinical gait laboratories, or Inverse Kinematics (IK), which is mainly used for musculoskeletal research. In both approaches, joint centre locations are required to compute joint angles. The hip joint centre (HJC) in DK models can be estimated using predictive or functional methods, while in IK models can be obtained by scaling generic models. The aim of the current study was to systematically investigate the impact of HJC location errors on lower limb joint kinematics of a clinical population using DK and IK approaches. Subject-specific kinematic models of eight children with cerebral palsy were built from magnetic resonance images and used as reference models. HJC was then perturbed in 6mm steps within a 60mm cubic grid, and kinematic waveforms were calculated for the reference and perturbed models. HJC perturbations affected only hip and knee joint kinematics in a DK framework, but all joint angles were affected when using IK. In the DK model, joint constraints increased the sensitivity of joint range-of-motion to HJC location errors. Mean joint angle offsets larger than 5° were observed for both approaches (DK and IK), which were larger than previously reported for healthy adults. In the absence of medical images to identify the HJC, predictive or functional methods with small errors in anterior-posterior and medial-lateral directions and scaling procedures minimizing HJC location errors in the anterior-posterior direction should be chosen to minimize the impact on joint kinematics.

Seventeen species of Parahebe are recognised for New Zealand, an increase of six from the most recent Flora treatment. The new species result from division of P. catarractae sens. lat. into P. catarractae (now confined to Fiordland), P. martinii (Marlborough), and P. lanceolata (North Island and North‐West Nelson); two new species (P. senex in North‐West Nelson and P. spectabilis in the Takitimu Range); and acceptance of P. brevistylis and P. laxa at species rank. We also describe two subspecies in P. cheesemanii: subsp. cheesemanii from Nelson and subsp. flabellata from Arthur's Pass. Species limits are discussed in terms of morphological and flavonoid evidence, and some limited data on natural and artificial hybrids are also presented. Problems of the generic limits in the Veroniceae are discussed in relation to Parahebe. Parahebe appears to be paraphyletic and future changes in nomenclature are likely. This treatment covers the New Zealand plants treated as Parahebe in recent Floras.

Physiotherapy is one of the effective treatments for tendinopathy, whereby symptoms are relieved by changing the biomechanical environment of the pathological tendon. However, the underlying mechanism remains unclear. In this study, we first established a model of progressive tendinopathy-like degeneration in the rabbit Achilles. Following ex vivo loading deprivation culture in a bioreactor system for 6 and 12 days, tendons exhibited progressive degenerative changes, abnormal collagen type III production, increased cell apoptosis, and weakened mechanical properties. When intervention was applied at day 7 for another 6 days by using cyclic tensile mechanical stimulation (6% strain, 0.25 Hz, 8 h/day) in a bioreactor, the pathological changes and mechanical properties were almost restored to levels seen in healthy tendon. Our results indicated that a proper biomechanical environment was able to rescue early-stage pathological changes by increased collagen type I production, decreased collagen degradation and cell apoptosis. The ex vivo model developed in this study allows systematic study on the effect of mechanical stimulation on tendon biology.

The frequent occurrence of gender dimorphism has long been recognised as one of the distinctive features of the New Zealand flora. We list 83 seed plant genera in which gender dimorphism occurs, and document habit, pollination, and dispersal characters for each genus. This means that gender dimorphism is represented in 23% of the genera in the flora; however, not all of these genera are uniformly dimorphic in gender—40% of them include some species or populations that lack gender dimorphism. We estimate that gender dimorphism has arisen autochthonously in 17 of the 83 genera— therefore, gender dimorphism evolved elsewhere in most cases (80%), and was established in New Zealand by subsequent migration. A comparison of the genera in which gender dimorphism occurs with the remainder of the flora shows that gender dimorphism is strongly correlated with fleshy fruits, and with woody habits. No correlation was found between gender dimorphism and pollination mode, perhaps because relatively unspecialise...

Sexual polymorphisms in Narcissus triandrus (Amaryllidaceae): is this species tristylous?

Inbreeding depression caused by self-fertilisation was examined in the gynodioecious shrub Hebe subalpina under two planting regimens, non-competitive and competitive. We found differences among families in the magnitude of inbreeding depression, ranging from 0.31 to 0.63. On average, outcrossed progeny grew nearly twice as large as selfed progeny, and the coefficients of variation (CVs) for dry mass were lower for outcrossed progeny than selfed progeny within the non-competitive regimen. Planting regime had a highly significant effect on dry mass, such that plants grown in the competitive regimen were an order of magnitude smaller than those in the non-competitive regimen, and they also had higher CVs. However, planting regimen did not significantly affect the magnitude of inbreeding depression. Our results suggest that intrinsic differences exist in the growth rate of selfed and outcrossed individuals, and that inbreeding depression helps to maintain females at a high frequency in the populatio...

Nuclear receptors (NRs) are a family of ligand-modulated transcription factors with significant therapeutic relevance from metabolic disorders and inflammation to cancer, neurodegenerative, and psychiatric disorders. Drug discovery efforts are typically concentrated on modulating the natural ligand action within the ligand-binding pocket (LBP) in the C-terminal ligand-binding domain (LBD). Drawbacks of LBP-based strategies include physiological alterations due to disruption of ligand binding and difficulties in achieving tissue specificity. Furthermore, the lack of a "pure" and predictable mechanism of action predisposes such intervention toward drug resistance. Recent outstanding progress in our understanding of NR biology has shifted the focus of drug discovery efforts from inside to outside the LBP, affording consideration to the interaction between NRs and coactivator proteins, the interaction between NRs and DNA and the NRs' ligand-independent functions. This review encompasses such currently available NR non-LBP-based interventions and their potential application in therapy or as specific tools to probe NR biology.

Mechanical loading is believed to be a critical factor in the development and treatment of knee osteoarthritis. However, the contact forces to which the knee articular surfaces are subjected during daily activities cannot be measured clinically. Thus, the ability to predict internal knee contact forces accurately using external measures (i.e., external knee loads and muscle electromyographic [EMG] signals) would be clinically valuable. We quantified how well external knee load and EMG measures predict internal knee contact forces during gait. A single subject with a force-measuring tibial prosthesis and post-operative valgus alignment performed four gait patterns (normal, medial thrust, walking pole, and trunk sway) to induce a wide range of external and internal knee joint loads. Linear regression analyses were performed to assess how much of the variability in internal contact forces was accounted for by variability in the external measures. Though the different gait patterns successfully induced significant changes in the external and internal quantities, changes in external measures were generally weak indicators of changes in total, medial, and lateral contact force. Our results suggest that when total contact force may be changing, caution should be exercised when inferring changes in knee contact forces based on observed changes in external knee load and EMG measures. Advances in musculoskeletal modeling methods may be needed for accurate estimation of in vivo knee contact forces.

The objective of this work is to evaluate differences in trabecular bone (TB) texture between subjects with and without tibiofemoral cartilage defects using a variance orientation transform (VOT) method. A case-control study was performed in subjects without radiographic knee osteoarthritis (OA) (KL grade2) matched on sex, BMI, age, knee compartment, and meniscectomy where cases (n = 28) had cartilage defects (grade ≥2) and controls (n = 28) had no cartilage defects (grade2). Cartilage defects were assessed from MRI using validated methods. The VOT was applied to TB regions selected on medial and lateral compartments in knee X-rays and fractal signatures (FS) in the horizontal (FS(H) ) and vertical (FS(V) ) directions, and along the roughest part of TB (FS(Sta) ) and texture aspect ratio signatures (StrS), at different trabecular image sizes (0.30-0.70 mm) were calculated. Compared with controls, FS(V) for cases were higher (p 0.011) at image sizes 0.30-0.40 mm and 0.45-0.55 mm in the medial compartment. In the lateral compartment, FS(H) and FS(Sta) for cases were higher (p 0.028) than those for controls at 0.30-0.40 mm and 0.45-0.55 mm, while FS(V) was higher (p 0.02) at 0.30-0.40 mm. TB texture roughness was greater in subjects with cartilage defects than in subjects without, suggesting thinning and fenestration of TB occur early in OA and that the VOT identifies changes in TB in knees with early cartilage damage. No differences in StrS (p 0.05) were found.

Procedures are described for partitioning the selfing rate into contributions resulting from the different modes of chasmogamous selfing-geitonogamous, facilitated, prior, competing, and delayed-and for examining several functional aspects of self-fertilization associated with the different modes-reproductive assurance, degree of seed and pollen discounting, and relative abilities of cross- and self-pollen to fertilize ovules. The procedures involve floral manipulations-e.g., exclusion of pollinators, emasculation, and covering of stigmas-and typically require joint estimation of the mating system parameters in manipulated and unmanipulated plants. Two methods of mating system estimation are discussed, the first in which manipulations and selfing rate estimates are made using random parent plants that are resident in the population, and the second using plants with unique genotypes introduced from a separate population. The asymptotic variances of estimators for the different modes of selfing are compared...

Many functional-ecological, morphological, and physiological-factors affect the occurrence of selffertilization. Six modes of self-pollination are distinguished. These differ in whether they utilize specialized flowers, whether they involve the transfer of pollen within or between flowers, whether they are autonomous or mediated by vectors, and their timing relative to opportunities for outcrossing. The various modes of selfing are subject to different structural constraints. Prepotency, the preferential success of cross-pollen in achieving fertilizations when it competes with self-pollen, influences the frequency of selffertilization in some species. The amount of self-fertilization may depend on environmental conditions and the vector species visiting each flower and may vary among the flowers of one plant. To gain information on the prevalence of autonomous self-pollination, 66 species for which the degrees of selfcompatibility and autofertility (seed set in isolation) have been published were surveyed...

I present a phenotypic model of the selection of self-fertilization that applies to any mode of selfpollination. A novel factor, seed discounting-the loss of outcrossing maternal fitness accompanying an increase in self-fertilization-is introduced, and pollen discounting is reformulated. The model incorporates the effects of five principal factors-the cost of meiosis, inbreeding depression, reproductive assurance, and seed and pollen discounting. The model indicates that either complete cross- or selffertilization is selected, depending on the values of the parameters, but a number of additional factors can lead to intermediate frequencies of self-fertilization. Specific conditions for the selection of each mode of chasmogamous self-pollination and the effects of some special circumstances are derived by substituting the appropriate values of seed and pollen discounting in the general model. Geitonogamy and facilitated selfing are primarily nonadaptive by-products of mechanisms for outcrossing. Delayed se...

The relative success of fruit from paired self- and cross-pollinations was examined in Phormium tenax when the contrasted pollinations were separated by different distances on the same and different inflorescences. We determined whether the retention of selfed fruits differed from that of crossed fruits and whether it depended on the level of competition with crossed fruit, the number of seeds per fruit, and/or the presence of earlier developing fruit. We found that the success of selfed fruits is determined by the degree of competition with crossed fruits and may be an expression of self-incompatibility. Competition-dependence of the abscission of selfed flowers has not been documented previously. It is parallel to cryptic self-incompatibility in which individual self-pollen grains are not as successful as cross-pollen when competing on the same pistil. The competition-dependent abscission of self-pollinations considered here, however, operates at the level of whole flowers. The phenomenon of competition-dependent abscission of selfed flowers in P. tenax also has implications for the measurement and interpretation of self-incompatibility in other species. Self-incompatibility is a quantitative phenomenon. The facultative success of selfing shows that the effective strength of self-incompatibility can be highly susceptible to the conditions of competition under which it is measured. The competition-dependent abscission of selfed flowers allows a high level of outcrossing to be achieved while it assures seed set when pollinations are scarce. Several other causes of intermediate selfing frequencies can also be explained by this "best- of-both-worlds" hypothesis.

The properties of selection restricted by single and multiple constraints are examined by using the Lagrange and Kuhn-Tucker conditions of calculus. We show for a general set of fitness equations containing any number of strategy components and subject to any single differentiable equality constraint that the marginal fitnesses of any two strategy components are equal at the evolutionarily stable strategy (ESS) when expenditures are measured in the same units, those of a binding constraint. Equal marginal advantages are a necessary, though not usually a sufficient, condition for an interior ESS. When selection is operating under more than one constraint, the marginal fitnesses of any two strategy components are equal at the ESS whenever both components are affected by only one, and the same, binding constraint. The equalization of marginal fitnesses allows the positions of constrained fitness maxima to be explored in theoretical models or empirical tests and is a convenient heuristic for understanding selection.

Stigmatic exudate-eating chironomid flies (Smittia) and pollen-eating halodid beetles are the most common visitors to flowers ofPseudowintera colorata. Plants are self-incompatible. After selfing pollen tubes penetrate the nucellus; chase pollination experiments show that the incompatibility reaction occurs before fertilization. When pollen is applied to stigmas, the exudate dries rapidly and does not usually reappear. A review of anthophytes suggests that their common ancestor around 200 mya was bisexual and pollinated at least in part by nectar-seeking insects, possibly including flies. The angiosperm stigma appears to have evolved from a pollination drop mechanism via an adaxial stigmatic surface.

Temporal patterns of variability in the longevity of the male and female phases of individual flowers and in the gender expression of plants of a dichogamous New Zealand tree,Pseudowintera colorata (Winteraceae), were documented in field studies. Two measures for the duration of phases in a dichogamous flower are distinguished; the nominal phases based on morphological features of the flower, and the effective phases reflecting the duration of their functions. Flower and phase longevity and phenotypic gender varied considerably throughout the season and among individuals. Temporal variability in phenotypic gender was loosely synchronized among the 12 plants sampled. Three effects of an environmental factor (temperature) were noted. First, increased temperatures shortened the duration of the female phase but had no effect on the duration of the male phase. Second, pollination frequency was positively correlated with temperature. These results indirectly suggest that increased pollination may shorten the duration of the female phase. Third, average population maleness, measured as the proportion of open flowers in the population on a given day which were in the male phase, was positively correlated with temperature. It is postulated that temperature indirectly influences temporal patterns of gender expression in the population through its differential effects on the longevity of the male and female phases in individual flowers. A theoretical model of bet-hedging shows that, if the direction of an environmental effect on the proportions of the sexual phases is irreversible, selection favours asynchronous dichogamy and reduces the temporal variability as much as possible. If the direction of the response is reversible, heterodichogamy is favoured.

Qualitative methods of obtaining phylogenies seek distinct classes of characters that collectively are common, yet individually are insufficiently improbable that they provide reliable indications of monophyly. Multi-residue gaps (insertions or deletions) in DNA and protein sequences are easily recognised and are available in diverse organisms and loci. They are likely to experience few homoplasies, because these require two separate events to be matched in both starting position and length. Two tests of the ability of multi-residue gaps to recognise clades are conducted. (1) Among the 10.76 kb of noncoding DNA sequences from the ψη-globin region of 5 primates, there are 7 analysable multi-nucleotide gaps. These provide a corroborated and noncontradictory, fully resolved gene tree of hominoids. (2) Among the 35 amino acid sequences of globin chains available in 1978, there are 9 nonoverlapping multi-amino acid gaps. These indicate 8 noncontradictory divisions that agree with recognised taxa and gene categories. In the 412 realigned globin sequences available in 1989, 8 of the gaps are still analysable. These show a maximum of two homoplasies among the 8 × 412 = 3296 species-characters. Multi-residue gaps have a high potential to indicate clades. They could be used to reduce the computing labour required in a quantitative study or pooled from different data sets to examine particularly important or difficult phylogenetic questions.

Models of evolutionarily stable strategies are presented, which were designed to determine whether the disadvantage of anisogamous biparental sex is due to the cost of male allocation or to the cost of meiosis. The results show that (1) the cost of biparental sex is due to gene sharing given mutations increasing the proportion of non-cleistogamous parthenogenetic ova in cosexual individuals and (2) the cost of biparental sex is due to male allocation given mutations increasing somatic reproduction in cosexual individuals and mutations increasing partial pathenogenesis in dioecious females. It is suggested that, in general, the cost of biparental sex is due to male allocation when mutations that increase uniparental reproduction affect events before the male-allocation decision, and that the cost of biparental sex is due to gene sharing when mutations that increase uniparental reproduction affect events that come after the male-allocation decision.

The hypothesis ofHenriques andFernandes that several Iberian species ofNarcissus (Amaryllidaceae) are tristylous is reconsidered. Contrary to the opinion ofBateman and most subsequent authors, we believe that the available evidence indicates that some populations ofN. triandrus andN. fernandesii, at least, are tristylous; other populations ofN. triandrus are distylous.Hugonia cf.penicillanthemum (Linaceae) from new Caledonia is distylous, but it remains possible that other species ofHugonia are tristylous. The disputed occurrence of heterostyly in S. African species ofBauhinia (Leguminosae),Cleome (Capparaceae) andAneilema (Commelinaceae), and inAgelaea (Connaraceae) is discussed.

Estrogen receptors are therapeutic intervention targets for diseases such as osteoporosis and breast cancer with both tamoxifen and raloxifene established as clinical estrogen receptor antagonists. We report a series of novel selective estrogen receptor modulators (SERMs) whose structures are based on a flexible core scaffold differing from the triphenylethylene of tamoxifen analogues through the insertion of a benzylic methylene group as a flexible spacer between the aryl ring C and the ethylene group. A facile synthesis of the target compounds utilises the titanium tetrachloride/zinc mediated McMurry coupling reaction. Successive introduction onto the parent scaffold of hydroxyl functional groups afforded a series of increased potency ligands for the ER - essentially exploring the predicted in vivo metabolic activation of such aromatic SERM ligands. This second generation compound series demonstrated high antiproliferative potency against the MCF-7 human breast cancer cell line, with low cytotoxicity. High ER binding affinity (IC50 20 nM) together with up to 12 fold ERalpha/beta selectivity was also observed. In addition, the compounds displayed antiestrogenic effects at 40 nM when evaluated in the Ishikawa cell line with little estrogenic stimulation. Representative ligands were shown to be pro-apoptotic in human MCF-7 cells in a FACS based assay. Comparison of the docked structure obtained for the most active compound with the X-ray crystal structure reported for the complex of ERalpha and 4-hydroxytamoxifen, predict that these ligands bind in an antiestrogenic manner with some differences being observed in the benzylic Ring C orientation, as expected. This work further demonstrates the tolerance of the estrogen receptor towards flexible modulators.

Structure-based and ligand-based methods are used to derive predictive models in de novo drug design. Structure-based methods rely exclusively on prior knowledge of a protein structure to derive novel ligands, while ligand-based methods are traditionally used when no protein structure is available. Where there is sufficient information, these methods can be used in conjunction to increase the accuracy of simulation and enhance the drug design process. This review presents developments in the integration of these methods for de novo drug design, and recent results from both systems are highlighted.

In outcrossing hermaphrodite plants, the separate functions of pollen dispersal and pollen receipt may interfere with one another so that fitness as a paternal or maternal parent is compromised (van der Pijl, 1978; Bawa and Opler, 1975; Lloyd and Yates, 1982; Lloyd and Webb, 1986; Webb and Lloyd, 1986; Bertin and Newman, 1993; Harder and Barrett, 1995). This is particularly likely in flowers in which the sex organs are close together and mature at the same time. Interference can potentially take several forms, including the obstruction by pistils of efficient pollen dispatch by pollinators, stamens restricting access by pollinators to stigmas, thus reducing pollen deposition, and the deleterious effects of self-pollination on maternal function due to stigmatic, stylar, or ovular clogging. Although there is some experimental evidence for self-pollen interference (Shore and Barrett, 1984; Barrett and Glover, 1985; Bertin and Sullivan, 1988; Palmer et al., 1989; Waser and Price, 1991; Scribailo and Barrett, 1994), the other two forms of pollen-pistil interference have seldom been investigated (see, however, Barrett and Glover, 1985; Kohn and Barrett, 1992a).

Since heterostyly became well known over a century ago, botanists have consistently proposed that its adaptive significance lies in the encouragement it provides for outcrossing. Darwin (1877, p. 258) for example, wrote that “We may feel sure that plants have been rendered heterostyled to ensure cross-fertilization, for we know that a cross between the distinct individuals of the same species is highly important for the vigour and fertility of the offspring.” There has, however, been a variety of opinions expressed as to precisely how heterostyly ensures cross-fertilization.

Charles Darwin was fascinated by the phenomenon of heterostyly. He described (1862, 1877) how he first thought that pin and thrum plants of Primula species represented female and male sexes respectively, but found that they were both functionally hermaphroditic. He demonstrated the infertility of self-pollinations and crosses between plants of the same form, and concluded that the two forms, although hermaphrodites, are “related to each other like males and females… [because plants of each form]… must unite with one of the other form” (Darwin 1862)3.

It is generally recognized that biparental reproduction experiences a "cost" in comparison with uniparental reproduction by either asexual means or self-fertilization. However, less agreement exists on the nature and size of the cost. The cost of cross-fertilization (or less formally, the cost of sex) may arise from two different sources. Williams (1971) proposed that crossfertilizing individuals are at a disadvantage because they contribute only one set of genes to each offspring, whereas uniparentally reproducing individuals contribute two sets. If the genetic cost is measured as the relative loss of fitness from cross-fertilization compared with uniparental reproduction, the gene halving constitutes a 50% loss of fitness, the "cost of meiosis." In the same publication, Maynard Smith (1971a) postulated that biparental organisms are disadvantaged because they spend resources on producing males that do not contribute towards raising young. This allocation cost, the "cost of males," is also precisely 50% if parents invest equally in male and female offspring. The alternative costs of sex apply in different circumstances, depending on the order in which decisions are made on investing in male and female offspring (or gametes) and on reproducing uniparentally or biparentally (Lively and Lloyd 1990). When the decision on how much to invest in the sexes is made first, the subsequent mode of reproduction does not affect the previous sex allocations, and there is no cost of males. A 50% cost of meiosis is then experienced. The cost of meiosis applies to asexual reproduction via embryos in cosexes (parthenogenesis in animals, agamospermy in seed plants), and to open flower (chasmogamous) self-fertilization in plants. However, when the decision to reproduce uniparentally is made first, the cost of meiosis is fully retrieved because the double contribution to the offspring is exactly canceled by the loss of the outcrossing male contribution. The cost of males is experienced unless males contribute to parental care (Maynard Smith 197 lb). The cost of males applies to somatic asexuality (vegetative reproduction in plants, budding in animals), embryonic asexuality by females of dioecious populations, and cleistogamous self-fertilization in plants. The cross-fertilizing components of reproduction may not occur randomly among all members of a population. One source of nonrandom mating is biparental inbreeding through the mating of relatives. In many flowering plants, for example, both seeds and pollen are dispersed very locally so that adjacent relatives mate disproportionately (Handel 1983; Levin 1988). A proportion, r, of the genes of cross-fertilizing relatives are identical by descent from a common ancestor. Several authors therefore have suggested that a gene in an individual that crosses with a relative obtains an indirect contribution to its inclusive fitness in addition to the direct contribution to offspring. Hence, the cost of meiosis is reduced in proportion to the relatedness of the inbreeding relatives, from 1/2 to 1/2(1 r) (Barash 1976; Maynard Smith 1978; Solbrig 1979; Lloyd 1980; Williams 1980; Uyenoyama 1986, 1987; Yahara 1992). It is this conclusion that is reexamined here. We concentrate our attention on self-fertilization within open flowers, which Yahara (1992) considered, with some changes to the symbols. Consider a population in which individuals with