A structural biologist's view of the oestrogen receptor

Here we review the results that have emerged from our structural studies on the oestrogen receptor ligand-binding domain (ER-LBD). The effects of agonists and antagonists on the structure of ER- and ERβ-LBDs are examined. In addition, the findings from structural studies of ER-LBD in complex with peptide fragments corresponding to the NR-box II and III modules of the p160 coactivator TIF2 are discussed in the context of the assembly of ER:coactivator complexes. Together these studies have broadened our understanding of ER function by providing a unique insight into ER's ligand specificity, it's ability to interact with coactivators and the structural changes that underlie receptor agonism and antagonism.     

The role of replication studies in ecology

Recent large‐scale projects in other disciplines have shown that results often fail to replicate when studies are repeated. The conditions contributing to this problem are also present in ecology, but there have not been any equivalent replication projects. Here, we survey ecologists' understanding of and opinions about replication studies. The majority of ecologists in our sample considered replication studies to be important (97%), not prevalent enough (91%), worth funding even given limited resources (61%), and suitable for publication in all journals (62%). However, there is a disconnect between this enthusiasm and the prevalence of direct replication studies in the literature which is much lower (0.023%: Kelly 2019) than our participants' median estimate of 10%. This may be explained by the obstacles our participants identified including the difficulty of conducting replication studies and of funding and publishing them. We conclude by offering suggestions for how replications could be better integrated into ecological research.     

Structure-activity delineation of quinones related to the biologically active Calothrixin B

Quinones such as Calothrixins A and B display a range of biological properties. As part of our ongoing studies to elucidate the mechanism of action of the Calothrixins, several related quinones were synthesized and tested for biological activity. The results of the structure-activity relationship (SAR) studies are reported here.     

DNA修复酶的结构和功能

DNA修复酶是一类能保护生物体免受各种DNA损伤的毒性效应和保证遗传信息完整性的重要酶蛋白。近年来对DNA修复酶晶体结构的研究揭示了一些结构基序参与了酶蛋白与特定DNA损伤的识别过程,这些研究结果促进了对修复特定DNA损伤的作用机理和结构基础的认识和了解。本文综述了这方面的研究进展。     

Otolith Shape Analysis as a Tool for Species Identification and Studying the Population Structure of Different Fish Species

An analysis and a comparison of the methods of geometric morphometrics as applied to fish species identification and to studies on the population structure of fish stocks based on peculiarities of the otolith shape are performed. A review of the geometric morphometric methods used in studies on fish otoliths is provided. The results of our own research on possible utilization of elliptical Fourier analysis for species identification are also described.     

The habitat sampling and analysis paradigm has limited value in animal conservation: A prequel

In this essay, I make the case that our studies of wildlife and habitat are largely decoupled from any meaningful relationship to the distribution of the study species. The field that we broadly classify as wildlife–habitat relationships is characterized by an increasing number of studies that gather additional data on phenomena that are already well studied. I offer that unless we make changes to the fundamental aspect of study design, our studies will fail to advance conservation of species. The current habitat sampling and analysis paradigm involves identification of a convenient study area, drawing samples from the usual list of parameters, conducting a series of statistical analyses, comparing findings to other studies, and justifying publication by extrapolating findings to some unspecified larger area. Recommendations for management are usually vague and are seldom tested for efficacy. Most of our habitat studies have little relevance to the target species with regard to viability. Attempts to translate the “best scientific information” into a set of management guidelines for a species produce one size fits all documents. I describe how we usually compromise our studies well before data collection by failing to establish a cogent framework for sampling from an ecologically meaningful unit of a population, but rather sample based on funding priorities and convenience. Specifying the sampling universe for a species sets the stage for properly establishing the sampling frame. Although we always have a target population, that target is often the result of personal, political, or administrative interest, but has little to do with biological reality. I review various intraspecies levels that could be a focus for study, including subspecies and especially ecotypes. Although making assumptions about our study species and habitat parameters is a necessary step, carrying forward untested assumptions from previous studies and failing to test new ones substantially negates the application of research results to meaningful management actions. I include recommendations for enhancing studies of wildlife and habitat with the intent of altering the current norm of wildlife–habitat studies. © 2012 The Wildlife Society.     

The discovery of a novel calcium channel blocker related to the structure of potassium channel opener cromakalim

During our studies aimed at the identification of novel analogs of the potassium channel opener cromakalim (3), we serendipitously observed pyranoquinoline 4 to possess pure calcium channel blocking activity. The results of the studies conducted to confirm the calcium channel blocking mechanism of 4 are reported in this paper.     

Sample size and sampling error in geometric morphometric studies of size and shape

Geometric morphometric studies are increasingly becoming common in systematics and palaeontology. The samples in such studies are often small, due to the paucity of material available for analysis. However, very few studies have tried to assess the impact of sampling error on analytical results. Here, this issue is addressed empirically using repeated randomized selection experiments to build progressively smaller samples from an original dataset of ∼400 vervet monkey (Cercopithecus aethiops) skulls. Size and shape parameters (including mean size and shape, size and shape variances, angles of allometric trajectories) that are commonly used in geometric morphometric studies, are estimated first in the original sample and then in the random subsamples. Estimates are then compared to give an indication of what is the minimum desirable sample size for each parameter. Mean size, standard deviation of size and variance of shape are found to be fairly accurate even in relatively small samples. In contrast, mean shapes and angles between static allometric trajectories are strongly affected by sampling error. If confirmed in other groups, our findings may have substantial implications for studies of morphological variation in present and fossil species. By performing rarefaction analyses like those presented in our study, morphometricians can be easily provided with important clues on how a simple but crucial factor like sample size can alter results of their studies.     

Control of adenovirus packaging

The results of studies of Adenovirus have contributed to our basic understanding of the molecular biology of the cell. While a great body of knowledge has been developed concerning Ad gene expression, viral replication, and effects on the infected host, the molecular details of the assembly process of Adenovirus particles are largely unknown. In this article, we would like to propose a theoretical model for the packaging and assembly of Adenovirus and present an overview of the studies that have contributed to our present understanding. In particular, we will summarize the molecular details of the process for packaging of viral DNA into virus particles and highlight the events in packaging and assembly that require further study.     

Neuroimaging and neuroscience of emotional processes

In neurosciences, there is increasing interest in studying affective, emotional and social processes in humans and animals. What are the conceptual framework identified for these studies and the technical approaches undertaken? What information has already emerged from these studies? Which results have already been obtained and what are the researchers' goals? Can these neuroimaging analyses provide novel insights to improve our understanding of psychiatric disorders? These are some of the questions addressed in this concise overview of our knowledge in this domain.     

Patterns of septal biomineralization in Scleractinia compared with their 28S rRNA phylogeny: a dual approach for a new taxonomic framework

A molecular phylogeny of the Scleractinia is reconstructed from approximately 700 nucleotides of the 5'end of the 28S rDNA obtained from 40 species. A comparison of molecular phylogenic trees with biomineralization patterns of coral septa suggests that at least five clades are corroborated by both types of data. Agaricidae and Dendrophylliidae are found to be monophyletic, that is supported by microstructural data. Conversely, Faviidae and Caryophylliidae are found to be paraphyletic: Cladocora should be excluded from the faviids, whereas Eusmilia should be excluded from the caryophylliids. The conclusion is also supported by the positions, sizes and shapes of centres of calcification. The traditional Guyniidae are diphyletic, corroborating Stolarski's hypothesis 'A'. Some results from our most parsimonious trees are not strongly statistically supported but corroborated by other molecular studies and microstructural observations. For example, in the scleractinian phylogenetic tree, there are several lines of evidence (including those from our data) to distinguish a Faviidae–Mussidae lineage and a Dendrophylliidae–Agaricidae–Poritidae–Siderastreidae lineage. From a methodological standpoint, our results suggest that co-ordinated studies creating links between biomineralization patterns and molecular phylogeny may provide an efficient working approach for a re-examination of scleractinian classification. This goal is important because in the evolutionary scheme proposed by Wells that presently remains the basic framework in coral studies, patterns of septal microstructures are involved. Validating from molecular phylogenies a given microstructural character state as a potential synapomorphy for a clade is the only way to include fossils in the coral classification, an approach that should allow the unity of coral classification to be maintained up to the origin of the phylum in the Triassic times.     

Theoretical prediction of base sequence effects in DNA. Experimental reactivity of Z-DNA and B-Z transition enthalpies

Molecular modeling is used to study the sequence dependence of conformation and stability within helically regular duplex Z-DNA. The variations of conformation that are found are sufficiently important to be classified as a new type of polymorphism within the Z family. It is also demonstrated that certain sequences can adopt more than one of these polymorphic forms. Comparison with experimental studies of chemical reactivity within a natural DNA fragment, forced into a left-handed conformation, suggests that the results of our modeling may be used to explain the chemical reactivity observed. Comparison of the Z results with similar studies of the B form allow enthalpies of transition to be calculated as a function of base sequence.     

The safety and efficacy of breast implants for augmentation mammaplasty

This review of the efficacy and safety of breast implants was intended to focus on our current body of knowledge about these devices. There are informational gaps, but not all of these can be laid at the door of imperfect studies or failed scientific methods. Certain properties of the implants are still unmeasurable, immunologic investigation is still evolving, the cause of wound contraction is inexplicable here or in the burnscar contracture, and the indications for and results of this surgery necessarily are subjective. Still, there are a number of investigative avenues open to us, and our cumulative experience shows no reluctance on the part of plastic surgeons to initiate further studies.     

Meta-analysis of diagnostic test accuracy assessment studies with varying number of thresholds

Current meta-analytic methods for diagnostic test accuracy are generally applicable to a selection of studies reporting only estimates of sensitivity and specificity, or at most, to studies whose results are reported using an equal number of ordered categories. In this article, we propose a new meta-analytic method to evaluate test accuracy and arrive at a summary receiver operating characteristic (ROC) curve for a collection of studies evaluating diagnostic tests, even when test results are reported in an unequal number of nonnested ordered categories. We discuss both non-Bayesian and Bayesian formulations of the approach. In the Bayesian setting, we propose several ways to construct summary ROC curves and their credible bands. We illustrate our approach with data from a recently published meta-analysis evaluating a single serum progesterone test for diagnosing pregnancy failure.     

Morphogenesis of leaves and cones of male short-shoots of Ginkgo biloba L.

Although the subject of several studies, the phylogeny of Ginkgo biloba is still ambiguous. Most of the morphological and some palaeontological studies assume a close relationship to conifers, but other palaeontological studies regard the origin of Ginkgo biloba in groups that exhibit a pinnate bauplan like Peltaspermales or Dicranophyllales. This divergence has led to controversial interpretations of male sporangiophores and leaves. Attempting to resolve this, here we have investigated the male cones and leaves of short-shoots by SEM and light-microscopy. Our results indicate that the male sporangiophores are simple structures, and the observed formation of thickened cell walls at the sterile adaxial side of the sporangiophores, similar to the endothecium of the sporangia, gives weak support for a precursor of Ginkgo-sporangiophores that displayed simple male sporangiophores with radial arrangement of the sporangia. Thus, our interpretations of the male sporangiophores of Ginkgo biloba allude to a relationship with Coniferales, Gnetales and Cordaitales and reject a close relationship of Ginkgo biloba with pinnate groups like Cycadaceae, as assumed by some molecular studies. In contrast to previous studies on long-shoot leaves, our results on short-shoot leaves give no indication for a compound character of Ginkgo leaves. Moreover, we infer that Ginkgo leaves could be derived from a simple bauplan, by two modifications of the basic growth pattern of conifer leaves, assuming that the dissection of Ginkgo leaves is secondary. Although more comparative investigations are necessary, our results support a coniferophyte origin of the Ginkgoales.     

Pondering Poi Dog: Place and racial identification of multiracial Native Hawaiians

Given the very large proportion of Hawaiians who are multiracial, our research examines Native Hawaiian identification in mixed-race Hawaiian families. We use the 1990 US Census, which affords a unique look at racial identification because multiracial people were required to choose one race over another. The results show support for our argument that place plays a central role in Pacific identity processes, illustrated in this case among Hawaiians. We find that strong ties to Hawai‘i – the spiritual and geographic home of the Hawaiian population – are vital to the intergenerational transmission of Hawaiian identification in both continental and island multiracial families. We compare our results for multiracial Native Hawaiians to prior studies of American Indians and Asian Americans to identify any general patterns in correlates of racial identification choices. In each group, we find that familial and geographic relationships to the cultural and ancestral lands are strongly linked to racial identification.     

The use of serologic tests for the diagnosis of chlamydial infections

Serology is commonly used for the diagnosis of acute Chlamydia pneumoniae infections and also for the diagnosis of complicated Chlamydia trachomatis infections. Furthermore, recent sero-epidemiological studies have linked C. pneumoniae infection with several diseases traditionally considered non-infectious. The objectives of this mini-review are to critically review and discuss some selected analytical and methodological aspects, controversies and current problems in chlamydial serodiagnosis. To illustrate our views we present some original data of the comparison of current technologies. The review of the literature revealed high variability in methodologies applied to different studies. This observation was supported by our own data, which explains occasional conflicting clinical interpretation. Although the microimmunofluorescence (MIF) technique is generally considered as the gold standard for serodiagnosis of chlamydial infections, assay conditions are highly variable and hence pose a major problem in the interpretation of the results. For instance, many recent studies linking C. pneumoniae and atherosclerosis have utilized MIF techniques with variable threshold criteria for the positivity, in combination with selection bias of cases and controls possibly leading to conflicting results. Variability of assay conditions is also a common problem with Western blots, and interpretation is problematic when both anti-C. pneumoniae and anti-C. trachomatis antibodies are present. Furthermore, there is a lot of disagreement in serological criteria applied to recently emerged enzyme immunoassay (EIA) techniques when these assays are used for acute and non-acute clinical conditions and their association with Chlamydiae. In conclusion, standardization of serological techniques and the development of uniform criteria for interpretation of serologic findings is necessary to increase our knowledge of the biology of Chlamydiae, pathogenesis of any chlamydial infection and chronic infections in particular.     

Conversion of microbial rhodopsins: insights into functionally essential elements and rational protein engineering

Technological progress has enabled the successful application of functional conversion to a variety of biological molecules, such as nucleotides and proteins. Such studies have revealed the functionally essential elements of these engineered molecules, which are difficult to characterize at the level of an individual molecule. The functional conversion of biological molecules has also provided a strategy for their rational and atomistic design. The engineered molecules can be used in studies to improve our understanding of their biological functions and to develop protein-based tools. In this review, we introduce the functional conversion of membrane-embedded photoreceptive retinylidene proteins (also called rhodopsins) and discuss these proteins mainly on the basis of results obtained from our own studies. This information provides insights into the molecular mechanism of light-induced protein functions and their use in optogenetics, a technology which involves the use of light to control biological activities.     

Experimental and computational studies of strain-conduction velocity relationships in cardiac tissue

Velocity of electrical conduction in cardiac tissue is a function of mechanical strain. Although strain-modulated velocity is a well established finding in experimental cardiology, its underlying mechanisms are not well understood. In this work, we summarized potential factors contributing to strain-velocity relationships and reviewed related experimental and computational studies. We presented results from our experimental studies on rabbit papillary muscle, which supported a biphasic relationship of strain and velocity under uni-axial straining conditions. In the low strain range, the strain-velocity relationship was positive. Conduction velocity peaked with 0.59 m/s at 100% strain corresponding to maximal force development. In the high strain range, the relationship was negative. Conduction was reversibly blocked at 118+/-1.8% strain. Reversible block occurred also in the presence of streptomycin. Furthermore, our studies revealed a moderate hysteresis of conduction velocity, which was reduced by streptomycin. We reconstructed several features of the strain-velocity relationship in a computational study with a myocyte strand. The modeling included strain-modulation of intracellular conductivity and stretch-activated cation non-selective ion channels. The computational study supported our hypotheses, that the positive strain-velocity relationship at low strain is caused by strain-modulation of intracellular conductivity and the negative relationship at high strain results from activity of stretch-activated channels. Conduction block was not reconstructed in our computational studies. We concluded this work by sketching a hypothesis for strain-modulation of conduction and conduction block in papillary muscle. We suggest that this hypothesis can also explain uni-axially measured strain-conduction velocity relationships in other types of cardiac tissue, but apparently necessitates adjustments to reconstruct pressure or volume related changes of velocity in atria and ventricles.     

Biological variability in biomechanical engineering research: Significance and meta-analysis of current modeling practices

Biological systems are characterized by high levels of variability, which can affect the results of biomechanical analyses. As a review of this topic, we first surveyed levels of variation in materials relevant to biomechanics, and compared these values to standard engineered materials. As expected, we found significantly higher levels of variation in biological materials. A meta-analysis was then performed based on thorough reviews of 60 research studies from the field of biomechanics to assess the methods and manner in which biological variation is currently handled in our field. The results of our meta-analysis revealed interesting trends in modeling practices, and suggest a need for more biomechanical studies that fully incorporate biological variation in biomechanical models and analyses. Finally, we provide some case study example of how biological variability may provide valuable insights or lead to surprising results. The purpose of this study is to promote the advancement of biomechanics research by encouraging broader treatment of biological variability in biomechanical modeling.