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PubMed2025

Harnessing Landscape Genomics to Evaluate Genomic Vulnerability and Future Climate Resilience in an East Asia Perennial.

In this era of rapid climate change, understanding the adaptive potential of organisms is imperative for buffering biodiversity loss. Genomic forecasting provides invaluable insights into population vulnerability and adaptive potential under diverse climatic conditions, thereby facilitating management interventions and bolstering shaping species-specific germplasm conservation strategies. We primarily employed landscape genomics approaches, leveraging single-nucleotide polymorphisms obtained through whole-genome resequencing of 201 individuals across 43 Rheum palmatum complex populations, to pinpoint adaptive variation and its significance in the context of future climates, delineate seed zones, and establish guidelines for ex situ germplasm conservation. The species complex exhibited strong signatures of local adaptation and differential genomic vulnerabilities across its distribution range, with eastern lineage populations facing significant maladaptation risks under future climate scenarios. Using diverse datasets of putatively adaptive loci and climate change scenarios, we delineated three distinct seed zones within the species' range, estimated varying sample sizes per zone to capture most adaptive diversity, and predicted shifts in seed zone centroids ranging from 48.3 to 359.3 km from historical distributions to mitigate climate change impacts. Collectively, our findings underscore the importance of integrating genomic and environmental data to forecast the adaptive trajectory of an East Asian perennial under anticipated climate changes, guide seed zone delineation for germplasm conservation and enhance population resilience. These results provide a blueprint for designing targeted conservation strategies and restoration plans in other imperilled species.

Climate Change↗

PubMedDate not supplied

Comparing the performance of FLUFF-BALL to SEAL-CoMFA with a large diverse estrogen data set: from relevant superpositions to solid predictions.

In this work a template-based molecular mechanistic superposition algorithm FLUFF (Flexible Ligand Unified Force Field) and an accompanying local coordinate QSAR method BALL (Boundless Adaptive Localized Ligand) are validated against the benchmark techniques SEAL (Steric and Electrostatic Alignment) and CoMFA (Comparative Molecular Field Analysis) using a large diverse set of 245 xenoestrogens extracted from the EDKB (Endocrine Disruptor Knowledge Base) maintained by NCTR (National Centre for Toxicological Research). The results indicate that FLUFF is capable of generating relevant superpositions not only for BALL but also for CoMFA, as both techniques give predictive QSAR models. When the BALL and CoMFA methods are compared, it is clear that the BALL algorithm met or even exceeded the results of the standard 3D-QSAR method CoMFA using alignments either from the tailor-made superposition technique FLUFF or the reference method SEAL. The FLUFF-BALL method can be easily automated, and it is computationally light, providing thus a good computational "sieve" capable of fast screening of large molecule libraries.

Algorithms↗

PubMedDate not supplied

A novel method for quantifying shape deformation applied to biocompatibility testing.

Cytotoxicity tests are important for the screening and evaluation of biocompatibility of artificial organs. Morphologic changes of cells that were contacted biomaterials or biomaterial extracts indicate their toxicity. However, information on cytotoxic effects is still obtained by subjective visual inspection of microscopic samples. In this article, a novel computer assisted method is introduced. The automatic analysis of digitized micrographs is achieved in several stages: segmentation, separation, classification, and measurement. The segmentation of the image is provided by a new local adaptive thresholding technique, which adapts the threshold window sizes onto local gray level distribution and yields optimal window sizes. The actual threshold is obtained by maximizing interclass variances and minimizing intraclass variance. For the separation of connected cells, the binarized samples are cleaned from "false" markers by morphologic filtering. The subsequent separation is a two phase approach. Information levels are generated top-down by successively applying an enhanced erosion operator, which yields markers and filters noise usually evolving from multiple erosions. The converse bottom-up integration of the eroded markers is performed by successively applying an enhanced dilation operator, which reconstructs the cells and prevents merging of already separated objects. The subsequent measuring provides quantitative parameters of the distribution of size and compactness of the cells contained within the sample. The method was evaluated by L-929 fibroblasts that were in contact with 0%, 5%, and 10% concentrations of ethanol. For each concentration, 268 images of the cell populations were captured. The obtained quantitative parameters are highly correlated to the common verbal description of morphologic changes. Therefore, the proposed automatic method has several advantages compared with subjective examinations. The results allow an objective comparison of the quantification of phenomena; the subjective influence of the observer is eliminated; and the laboratory staff is relieved of time consuming routine work.

Animals↗

PubMed1981

[Contribution to problems of the adaptation concept in pathology using the heart as an example (author's transl)].

The paper represents a contribution to the problems associated with the adaptation concept used in biology and medicine for which there does not yet exist an exact and generally accepted definition. Several aspects of the adaptation concept as it is applied in pathology (adaptation and disease, adaptation on the cellular level, adaptation and and optimation, systemic and local adaptation) are illustrated by means of the adaption of the heart to physiological and pathological condition, with particular attention being paid to questions of cellular adaptation. Finally, it is emphasized that knowledge of the structural and functional changes underlying the adaptation of the organism is of great importance to the prevention of diseases.

Adaptation, Physiological↗

PubMed2026

Signals of Natural Selection Across Regions of Low Recombination in Wild Populations of the Purple Sea Urchin, Strongylocentrotus purpuratus.

Structural variants (SVs) are increasingly recognized as important components of genetic architecture. Yet our understanding of the evolutionary forces maintaining SVs in natural populations is limited. Chromosomal inversions in particular can facilitate local adaptation in populations with high gene flow, including many marine species. The purple sea urchin (Strongylocentrotus purpuratus) is a powerful system to study these dynamics due to its high gene flow, lack of population structure, and broad latitudinal range. We analyzed whole genome sequence data from 137 individuals sampled across seven populations to identify regions of low recombination using scans for elevated linkage disequilibrium and genetic differentiation. Such regions may arise from structural variants, including chromosomal inversions. We identified nine regions showing signatures of reduced recombination, including three way genotype clustering, long range linkage, and hanging bridge patterns frequently associated with inversion polymorphisms. The regions were polymorphic within locations and along the species range with three loci showing concordant signatures of balancing and spatially heterogeneous selection based on enrichment of outliers and distinct patterns of allelic age. Additionally, these loci showed enrichment for genes associated with biomineralization and development. Our results provide the first evidence for regions of low recombination in the purple sea urchin genome, several of which display genomic signatures consistent with structural variants such as chromosomal inversions. These findings add to growing evidence that regions of reduced recombination constitute an important component of standing genetic variation in natural populations and may play a key role in adaptation to heterogeneous environments.

Strongylocentrotus purpuratus↗

PubMed2026

Cryptic serpentine divergence and substrate adaptation of Cardamine glauca in the Balkan Peninsula.

BACKGROUND AND AIMS: Serpentine soils represent one of the most challenging substrates for plant life due to skewed ratios of essential nutrients and toxic concentrations of metals. Plant adaptation to such conditions may lead to locally adapted edaphic ecotypes or, when reproductive barriers evolve, to distinct serpentine endemics. However, a third scenario may occur: cryptic edaphic divergence, where phenotypically similar lineages adapted to contrasting substrates exhibit deep genetic divergence. Here, we tested whether substrate-associated divergence reflects repeated serpentine adaptation or cryptic edaphic lineage divergence in Cardamine glauca (Brassicaceae) in Balkan peninsula - a hotspot of serpentine endemism in Europe. METHODS: We sampled and sequenced genomes of 43 individuals of C. glauca together with four individuals representing closely related taxa, C. plumieri and C. pancicii, from variable substrates across the Balkans. We combined phylogenomics, population genomic analyses of selection and a reciprocal transplant experiment to infer the most likely evolutionary scenario. KEY RESULTS: Phylogenomic analysis of 941 loci confirmed monophyly of C. glauca, including the local endemic C. pancicii, but revealed deep splits (∼2.2-3.2 Mya) between co-occurring serpentine and non-serpentine lineages. Population genomic analyses of replicated geographically proximate serpentine-non-serpentine population pairs demonstrated strong genome-wide differentiation and limited gene flow between edaphic types. Window-based analyses of local genomic divergence and tests for positive selection revealed candidate genes involved in ion transport, membrane transporter activity and metal homeostasis, consistent with the hypothesis of substrate-driven ecological adaptation. This was further supported by a significant substrate-of-origin fitness advantage in a reciprocal transplant experiment. CONCLUSIONS: Altogether, our results demonstrate that edaphic preferences may correspond with deep genetic divergence between similar-looking yet differently adapted lineages. The presence of cryptic edaphic lineages suggests that plant diversity may still be underestimated in genomically underexplored but edaphically diverse hotspots such as the Balkans.

Cardamine glauca↗

PubMed2025

Evolutionary legacy of the "living fossil" genus Parrotia (Hamamelidaceae): genomic insights into species divergence and polygenic adaptation.

Despite their long evolutionary history, the genomic basis of adaptation and speciation in "living fossil" plants remain largely unexplored. Parrotia, a Tertiary relict tree genus with two extant species, P. subaequalis and P. persica, exhibits a disjunct distribution between East Asia and West Asia. Here, we present the first chromosome-level assemblies for both species, confirmed their sibling relationship, and dated the speciation event to the early Miocene. The recent proliferation of long-terminal repeat retrotransposons has driven the genome expansion in P. subaequalis. We detected widespread heterogeneous genomic differentiation between species. Extensive signals of divergent selection, local adaptation, and elevated Ka/Ks ratios in Parrotia indicate that this genus has undergone adaptive evolution in distinct refugia, challenging the notion of it as an "evolutionary dead end". Our findings provide new insights into the genomic evolution, environmental adaptation, and speciation of this "living fossil" tree genus.

Genome, Plant↗

PubMed2005

A comparison of Monte Carlo dose calculation denoising techniques.

Recent studies have demonstrated that Monte Carlo (MC) denoising techniques can reduce MC radiotherapy dose computation time significantly by preferentially eliminating statistical fluctuations ('noise') through smoothing. In this study, we compare new and previously published approaches to MC denoising, including 3D wavelet threshold denoising with sub-band adaptive thresholding, content adaptive mean-median-hybrid (CAMH) filtering, locally adaptive Savitzky-Golay curve-fitting (LASG), anisotropic diffusion (AD) and an iterative reduction of noise (IRON) method formulated as an optimization problem. Several challenging phantom and computed-tomography-based MC dose distributions with varying levels of noise formed the test set. Denoising effectiveness was measured in three ways: by improvements in the mean-square-error (MSE) with respect to a reference (low noise) dose distribution; by the maximum difference from the reference distribution and by the 'Van Dyk' pass/fail criteria of either adequate agreement with the reference image in low-gradient regions (within 2% in our case) or, in high-gradient regions, a distance-to-agreement-within-2% of less than 2 mm. Results varied significantly based on the dose test case: greater reductions in MSE were observed for the relatively smoother phantom-based dose distribution (up to a factor of 16 for the LASG algorithm); smaller reductions were seen for an intensity modulated radiation therapy (IMRT) head and neck case (typically, factors of 2-4). Although several algorithms reduced statistical noise for all test geometries, the LASG method had the best MSE reduction for three of the four test geometries, and performed the best for the Van Dyk criteria. However, the wavelet thresholding method performed better for the head and neck IMRT geometry and also decreased the maximum error more effectively than LASG. In almost all cases, the evaluated methods provided acceleration of MC results towards statistically more accurate results.

Algorithms↗

PubMed2025

Conservation genomics of a threatened subtropical Rhododendron species highlights the distinct conservation actions required in marginal and admixed populations.

With the impact of climate change and anthropogenic activities, the underlying threats facing populations with different evolutionary histories and distributions, and the associated conservation strategies necessary to ensure their survival, may vary within a species. This is particularly true for marginal populations and/or those showing admixture. Here, we re-sequence genomes of 102 individuals from 21 locations for Rhododendron vialii, a threatened species distributed in the subtropical forests of southwestern China that has suffered from habitat fragmentation due to deforestation. Population structure results revealed that R. vialii can be divided into five genetic lineages using neutral single-nucleotide polymorphisms (SNPs), whereas selected SNPs divide the species into six lineages. This is due to the Guigu (GG) population, which is identified as admixed using neutral SNPs, but is assigned to a distinct genetic cluster using non-neutral loci. R. vialii has experienced multiple genetic bottlenecks, and different demographic histories have been suggested among populations. Ecological niche modeling combined with genomic offset analysis suggests that the marginal population (Northeast, NE) harboring the highest genetic diversity is likely to have the highest risk of maladaptation in the future. The marginal population therefore needs urgent ex situ conservation in areas where the influence of future climate change is predicted to be well buffered. Alternatively, the GG population may have the potential for local adaptation, and will need in situ conservation. The Puer population, which carries the heaviest genetic load, needs genetic rescue. Our findings highlight how population genomics, genomic offset analysis, and ecological niche modeling can be integrated to inform targeted conservation.

Rhododendron↗

PubMed1997

From clinical guidelines to quality assurance: the experience of Assistance Publique-Hôpitaux de Paris.

OBJECTIVES: The objectives of this study are: to present the history of the development of clinical guidelines in France. to present the implementation of a program of clinical guidelines in Assistance Publique-Hôpitaux de Paris (AP-HP), the regional public hospital system of the Paris metropolitan area, and to discuss the lessons learned from this program, which provide a basis for a better policy of guidelines at a national level. CONTENT: The objective of the AP-HP program is to promote the appropriate use of clinical guidelines and to evaluate their impact on quality of care and/or costs. Experiments such as controlled trials are used to test the effectiveness of some implementation strategies, to verify that guidelines do improve the process of care and to improve physician compliance with clinical guidelines. Guidelines are developed in a context of budget constraint, and the general aim of the program is to promote the more efficient use of available health resources. RESULTS: In a context of health care inflation, the desire of public authorities is to use guidelines as a tool for cost control strategy, either for ambulatory care or for hospitals. AP-HP experience shows that it is very difficult to develop a national program of clinical guidelines and to implement it in every hospital, as was done in France (but not clearly evaluated) in ambulatory care (under the name 'references médicales'). Guidelines need to be locally adapted, and the best implementation strategies depend on local resources, for example the existence of a pertinent information system. The role of financial incentives is present in French policies, and the role of the drug industry needs to be evaluated.

France↗

PubMed1978

Specificity of run training on VO2 max and heart rate cganges during running and swimming.

To further evaluate the specificity of aerobic training, maximum physiologic measures (VO2, VE, HR, and R) and submaximal exercise heart rate were determined in control (N = 8) and experimental (N = 11) subjects prior to and following 10-week interval run training. Experimental subjects significantly increased (P less than 0.01) treadmill VO2 max by 252 ml O2 or 6.3%. This was siginificantly larger (P less than 0.01) than the 87 ml O2 or 2.6% increase (P less than 0.05) observed during swimming. Max HR decreased significantly in both forms of exercise. In addition, heart rate at two submaximal work levels during running and swimming was significantly lower after training. No changes in metabolic and physiologic measures were demonstrated for the controls after the 10-wk period. These results further support the concept of the specificity of the metabolic adaptation to aerobic training and strongly suggest that local adaptations in skeletal muscle significantly contribute to improvement in VO2 max. However, running may produce a general training adaptation in maximal and submaximal heart rate.

Adolescent↗

PubMed1993

Automated three-dimensional image analysis of thick and overlapped clusters in cytologic preparations. Application to cytologic smears.

Methods are presented for automated analysis of thick and heavily overlapped regions of cytologic preparations, such as cervical/vaginal smears. Current systems are unable to process these regions although they contain diagnostically valuable information. We argue that analysis of such regions is inherently a three-dimensional (3-D) problem that cannot be solved reliably with conventional two-dimensional methods. Furthermore, this issue cannot be side-stepped by special thin preparation methods. Even with 3-D imaging, analysis of these regions is complicated by the high variability in the image gray level and textural features resulting from the uncontrollable cell overlaps and folds and large computational requirements. A novel approach based on 3-D imaging and adaptive 3-D analysis algorithms based on the principles of localization, adaptive data reduction and clustering theory is presented. It was successful in detecting and separating deeply embedded and overlapping nuclei, cytoplasmic folds and creases in thick and overlapped regions of conventional smears and special thin preparations.

Cytological Techniques↗

PubMed1992

Blood flow and muscle bio-energetics by 31P-nuclear magnetic resonance after local cold acclimation.

To clarify the origin of local cold adaptation and to define precisely its influence on muscle bio-energetics during local exercise, five subjects were subjected to repeated 5 degrees C cold water immersion of the right hand and forearm. The first aim of our investigation was therefore carried out by measuring local skin temperatures and peripheral blood flow during a cold hand test (5 degrees C, 5 min) followed by a 10-min recovery period. The 31P by nuclear magnetic resonance (31PNMR) muscle bio-energetic changes, indicating possible heat production changes, were measured during the recovery period. The second aim of our investigation was carried out by measuring 31PNMR muscle bioenergetics during handgrip exercise (10% of the maximal voluntary contraction for 5 min followed by a 10-min recovery period) performed both at a comfortable ambient temperature (22 degrees C; E) and after a cold hand test (EC), before and after local cold adaptation. Local cold adaptation, confirmed by warmer skin temperatures of the extremities (+30%, P less than 0.05), was related more to an increased peripheral blood flow, as shown by the smaller decrease in systolic peak [-245 (SEM 30) Hz vs -382 (SEM 95) Hz, P less than 0.05] than to a change in local heat production, because muscle bioenergetics did not vary. Acute local cold immersion decreased the inorganic phosphate:phosphocreatine (PC) ratio during EC compared to E [+0.006 (SEM 0.010) vs +0.078 (SEM 0.002) before acclimation and +0.029 (SEM 0.002) vs +0.090 (SEM 0.002) after acclimation respectively, P less than 0.05] without significant change in the PC:beta-adenosine triphosphate ratio and pH. Local adaptation did not modify these results statistically. The recovery of PC during E increased after acclimation [9.0 (SEM 0.2) min vs 3.0 (SEM 0.4) min, P less than 0.05]. These results suggested that local cold adaptation is related more to peripheral blood flow changes than to increased metabolic heat production in the muscle.

Acclimatization↗

PubMed1996

A model of temporal adaptation in fly motion vision.

A computational model is proposed to account for the adaptive properties of the fly motion system. The response properties of motion-sensitive neurons in the fly are modelled using an underdamped adaptive scheme to adjust the time constants of delay filters in an array of Reichardt detectors. It is shown that the increase in both temporal resolution and sensitivity to velocity change observed following adaptation to constant motion can be understood as a consequence of local adaptation of the filter time constants on the basis of the outputs of elementary motion detectors.

Adaptation, Ocular↗

PubMed2003

How to implement change in clinical practice.

Changing clinical practice is a major challenge. It is not acceptable simply to send out a new clinical guideline or care pathway and expect there to be a change in practice. This paper addresses the problems associated with the development of a clinical guideline and sets out a clear strategy for dissemination, implementation and evaluation in a way that should promote the successful change of practice. The first section examines the development of the guideline. National or international guidelines may well exist but local adaptation and refinement of those guidelines are required, along with a local summary document. Valid, reproducible, evidence-based, clear, logical, easily accessible guidelines need to be available after widespread local, multi-professional consultation. Second, prior to dissemination, there needs to be promotion among all the health professionals and families involved with the change in practice. Appropriate educational and multi-disciplinary interventions, highlighting and informing in workshops and preparing people for the changes are recommended. Recognising the barriers to implementation and change and addressing these locally is important. Once the guideline has been disseminated and implemented and the change in practice has occurred, full evaluation and ongoing audit of the changes in practice are required to sustain the changes.

Guideline Adherence↗

PubMed1990

The interplay of population dynamics and the evolutionary process.

Long-term maintenance of genetic diversity is affected by ecological forces that are driven in turn by current levels of genetic variation. The strength of population regulation and the consequent patterns of population fluctuations determine the likelihood of genetic changes considered pivotal for rapid speciation. However, genetic diversity in the susceptibility to regulatory forces can reduce the magnitude of such fluctuations and minimize the likelihood of genetic revolutions. A group of populations that experiences local extinctions and recolonizations may hold lower levels of genetic diversity than in the absence of such extinctions, but local adaption, which provides enhanced genetic diversity, can reduce the likelihood of local extinctions. Tightly regulated populations experience different selection pressures than poorly regulated populations, although tighter regulation itself can evolve. When genotypic variation affects the outcome of interspecific interactions on a local scale, this effect, coupled with appropriate spatial variation, can enhance the resilience of the interactive system.

Animals↗

PubMed1992

Local circuits for the control of leg movements in an insect.

To produce behaviour that is adaptive, local circuits in the CNS must transform mechanosensory signals from receptors on the body into changes in movement. Substantial insights into the mechanisms underlying these transformations can be obtained by analysing the local circuits of animals from which intracellular recordings can be made from identified neurones during behavior, thus allowing the complete pathways between inputs and outputs to be followed. In the locust (Schistocerca gregaria) these circuits contain both non-spiking and spiking local neurones so that it is possible to elucidate two basic issues of neuronal integration: (1) the operation of the reflex circuitry that must adjust locomotion, and (2) the integrative role of local circuits that use graded interactions in complex neuropil, perhaps even involving compartmentalized neurones.

Animals↗

PubMed2006

Replicated evolution of integrated plastic responses during early adaptive divergence.

Colonization of a novel environment is expected to result in adaptive divergence from the ancestral population when selection favors a new phenotypic optimum. Local adaptation in the new environment occurs through the accumulation and integration of character states that positively affect fitness. The role played by plastic traits in adaptation to a novel environment has generally been ignored, except for variable environments. We propose that if conditions in a relatively stable but novel environment induce phenotypically plastic responses in many traits, and if genetic variation exists in the form of those responses, then selection may initially favor the accumulation and integration of functionally useful plastic responses. Early divergence between ancestral and colonist forms will then occur with respect to their plastic responses across the gradient bounded by ancestral and novel environmental conditions. To test this, we compared the magnitude, integration, and pattern of plastic character responses in external body form induced by shallow versus open water conditions between two sunfish ecomorphs that coexist in four postglacial lakes. The novel sunfish ecomorph is present in the deeper open water habitat, whereas the ancestral ecomorph inhabits the shallow waters along the lake margin. Plastic responses by open water ecomorphs were more correlated than those of their local shallow water ecomorph in two of the populations, whereas equal levels of correlated plastic character responses occurred between ecomorphs in the other two populations. Small but persistent differences occurred between ecomorph pairs in the pattern of their character responses, suggesting a recent divergence. Open water ecomorphs shared some similarities in the covariance among plastic responses to rearing environment. Replication in the form of correlated plastic responses among populations of open water ecomorphs suggests that plastic character states may evolve under selection. Variation between ecomorphs and among lake populations in the covariance of plastic responses suggests the presence of genetic variation in plastic character responses. In three populations, open water ecomorphs also exhibited larger plastic responses to the environmental gradient than the local shallow water ecomorph. This could account for the greater integration of plastic responses in open water ecomorphs in two of the populations. This suggests that the plastic responses of local sunfish ecomorphs can diverge through changes in the magnitude and coordination of plastic responses. Although these results require further investigation, they suggest that early adaptive evolution in a novel environment can include changes to plastic character states. The genetic assimilation of coordinated plastic responses could result in the further, and possibly rapid, divergence of such populations and could also account for the evolution of genes of major effect that contribute to suites of phenotypic differences between divergent populations.

Acclimatization↗