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Molecular Biology and Evolution Sep 2021Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the...
Population genetic theory predicts that small effective population sizes (Ne) and restricted gene flow limit the potential for local adaptation. In particular, the probability of evolving similar phenotypes based on shared genetic mechanisms (i.e., parallel evolution), is expected to be reduced. We tested these predictions in a comparative genomic study of two ecologically similar and geographically codistributed stickleback species (viz. Gasterosteus aculeatus and Pungitius pungitius). We found that P. pungitius harbors less genetic diversity and exhibits higher levels of genetic differentiation and isolation-by-distance than G. aculeatus. Conversely, G. aculeatus exhibits a stronger degree of genetic parallelism across freshwater populations than P. pungitius: 2,996 versus 379 single nucleotide polymorphisms located within 26 versus 9 genomic regions show evidence of selection in multiple freshwater populations of G. aculeatus and P. pungitius, respectively. Most regions involved in parallel evolution in G. aculeatus showed increased levels of divergence, suggestive of selection on ancient haplotypes. In contrast, haplotypes involved in freshwater adaptation in P. pungitius were younger. In accordance with theory, the results suggest that connectivity and genetic drift play crucial roles in determining the levels and geographic distribution of standing genetic variation, providing evidence that population subdivision limits local adaptation and therefore also the likelihood of parallel evolution.
Topics: Animals; Fresh Water; Gene Flow; Genetic Drift; Genome; Smegmamorpha
PubMed: 33956140
DOI: 10.1093/molbev/msab144 -
JMIR Research Protocols May 2023Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing...
BACKGROUND
Obsessive-compulsive disorder (OCD) is a psychiatric syndrome characterized by unwanted and repetitive thoughts and repeated ritualistic compulsions for decreasing distress. Symptoms can cause severe distress and functional impairment. OCD affects 2% to 3% of the population and is ranked within the 10 leading neuropsychiatric causes of disability. Cortico-striatal-thalamo-cortical circuitry dysfunction has been implicated in OCD, including altered brain activation and connectivity. Complex glutamatergic signaling dysregulation within cortico-striatal circuitry has been proposed in OCD. Data obtained by several studies indicate reduced glutamatergic concentrations in the anterior cingulate cortex, combined with overactive glutamatergic signaling in the striatum and orbitofrontal cortex. A growing number of randomized controlled trials have assessed the utility of different glutamate-modulating drugs as augmentation medications or monotherapies for OCD, including refractory OCD. However, there are relevant variations among studies in terms of patients' treatment resistance, comorbidity, age, and gender. At present, 4 randomized controlled trials are available on the efficacy of memantine as an augmentation medication for refractory OCD.
OBJECTIVE
Our study's main purpose is to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of moderate to severe OCD. The study's second aim is to evaluate the effect of memantine on cognitive functions in patients with OCD. The third aim is to investigate if responses to memantine are modulated by variables such as gender, symptom subtypes, and the duration of untreated illness.
METHODS
Investigators intend to conduct a double-blind, randomized, parallel-group, placebo-controlled, monocenter trial to assess the efficacy and safety of memantine as an augmentative agent to a selective serotonin reuptake inhibitor in the treatment of patients affected by severe refractory OCD. Participants will be rated via the Yale-Brown Obsessive Compulsive Scale at baseline and at 2, 4, 6, 8, 10, and 12 months. During the screening period and T4 and T6 follow-up visits, all participants will undergo an extensive neuropsychological evaluation. The 52-week study duration will consist of 4 distinct periods, including memantine titration and follow-up periods.
RESULTS
Recruitment has not yet started. The study will be conducted from June 2023 to December 2024. Results are expected to be available in January 2025. Throughout the slow-titration period, we will observe the minimum effective dose of memantine, and the follow-up procedure will detail its residual efficacy after drug withdrawal.
CONCLUSIONS
The innovation of this research proposal is not limited to the evaluation of the efficacy and safety of memantine as an augmentation medication for OCD. We will also test if memantine acts as a pure antiobsessive medication or if memantine's ability to improve concentration and attention mimics an antiobsessive effect.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05015595; https://clinicaltrials.gov/ct2/show/NCT05015595.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
PRR1-10.2196/39223.
PubMed: 37166948
DOI: 10.2196/39223 -
International Journal of Implant... Feb 2019The outcome of the evaluation of impression techniques accuracy may improve the selection criteria for an ideal technique. The aim was to evaluate the accuracy of the...
BACKGROUND
The outcome of the evaluation of impression techniques accuracy may improve the selection criteria for an ideal technique. The aim was to evaluate the accuracy of the open and closed tray techniques for implant impressions, in a partially edentulous maxilla, replaced with a three-unit fixed partial denture, as well as to assess the effect of implants parallelism on accuracy.
MATERIAL AND METHODS
This is an experimental in vitro study to evaluate impressions accuracy of a simulated area restored with an implant retained FPD, using the open and closed tray implant impression techniques. The effect of implant position angulation, parallelism, and implant systems (Straumann, SIC Invent, Osstem) was also evaluated. Three custom-made acrylic resin test models were prepared with two parallel and two non-parallel implants, on either side of a maxillary arch. One hundred and ninety-two impressions were made using monophase VPS impression material. Their master casts were obtained and evaluated for the horizontal and vertical discrepancy. The casts were scanned using a model scanner. The distances between the two reference points were measured.
RESULTS
The Straumann and SIC Invent implants showed no statistically significant differences (Mann-Whitney U test), regarding accuracy for both the open and closed tray impression techniques (P = 0.667 and P = 0.472). There were no significant differences for the parallel and non-parallel implants (P = 0.323 and P = 0.814), respectively, while the Osstem system showed statistically significant differences for both the open and closed tray impression techniques (P = 0.035) and between the parallel and non-parallel implants (P = 0.045). For the vertical discrepancies, significant differences were detected (chi-square test) between the open and closed tray impression techniques (P = 0.037).
CONCLUSIONS
Within the limitations of this study, there were generally no significant differences between open and closed, although better results were obtained for the open tray techniques. On the use of the non-parallel implants, the open tray technique provided a better result than the closed tray technique.
PubMed: 30778790
DOI: 10.1186/s40729-019-0159-5 -
Evolutionary Bioinformatics Online 2018Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal... (Review)
Review
Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes-master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)-is carried out for this problem. Several procedures that optimize the use of the GPU's resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent sequential single-core implementation running on a recent Intel i7 CPU. This work can provide useful guidance to researchers in biology, medicine, or bioinformatics in how to take advantage of the parallelization on massively parallel devices and GPUs to apply novel metaheuristic algorithms powered by nature for real-world applications (like the method to solve the temporal dynamics of GRNs).
PubMed: 29662297
DOI: 10.1177/1176934318767889 -
Molecular Systems Biology Sep 2022Current strategies to improve the throughput of continuous directed evolution technologies often involve complex mechanical fluid-controlling system or robotic...
Current strategies to improve the throughput of continuous directed evolution technologies often involve complex mechanical fluid-controlling system or robotic platforms, which limits their popularization and application in general laboratories. Inspired by our previous study on bacterial range expansion, in this study, we report a system termed SPACE for rapid and extensively parallelizable evolution of biomolecules by introducing spatial dimensions into the landmark phage-assisted continuous evolution system. Specifically, M13 phages and chemotactic Escherichia coli cells were closely inoculated onto a semisolid agar. The phages came into contact with the expanding front of the bacterial range, and then comigrated with the bacteria. This system leverages competition over space, wherein evolutionary progress is closely associated with the production of spatial patterns, allowing the emergence of improved or new protein functions. In a prototypical problem, SPACE remarkably simplified the process and evolved the promoter recognition of T7 RNA polymerase (RNAP) to a library of 96 random sequences in parallel. These results establish SPACE as a simple, easy to implement, and massively parallelizable platform for continuous directed evolution in general laboratories.
Topics: Agar; Bacteria; Bacteriophages; Escherichia coli; Promoter Regions, Genetic
PubMed: 36129229
DOI: 10.15252/msb.202210934 -
Journal of Evolutionary Biology Jan 2021Non-native species experience novel selection pressures in introduced environments and may interbreed with native lineages. Species introductions therefore provide... (Comparative Study)
Comparative Study
Non-native species experience novel selection pressures in introduced environments and may interbreed with native lineages. Species introductions therefore provide opportunities to investigate repeated patterns of adaptation and introgression across replicated contact zones. Here, we investigate genetic parallelism between multiple introduced populations of the invasive marine mussel, Mytilus galloprovincialis, in the absence (South Africa and California) and presence of hybridization with a native congener (Mytilus planulatus in Batemans Bay and Sydney Harbour, Australia). Repeatability in post-introduction differentiation from native-range populations varied between genetically distinct Atlantic and Mediterranean lineages, with Atlantic-derived introductions displaying high differentiation (maxF > 0.4) and parallelism at outlier loci. Identification of long noncoding RNA transcripts (lncRNA) additionally allowed us to clarify that parallel responses are largely limited to protein-coding loci, with lncRNAs likely evolving under evolutionary constraints. Comparisons of independent hybrid zones revealed differential introgression most strongly in Batemans Bay, with an excess of M. galloprovincialis ancestry and resistance to introgression at loci differentiating parental lineages (M. planulatus and Atlantic M. galloprovincialis). Additionally, contigs putatively introgressed with divergent alleles from a closely related species, Mytilus edulis, showed stronger introgression asymmetries compared with genome-wide trends and also diverged in parallel in both Atlantic-derived introductions. These results suggest that divergent demographic histories experienced by introduced lineages, including pre-introduction introgression, influence contemporary admixture dynamics. Our findings build on previous investigations reporting contributions of historical introgression to intrinsic reproductive architectures shared between marine lineages and illustrate that interspecific introgression history can shape differentiation between colonizing populations and their hybridization with native congeners.
Topics: Animals; Biological Evolution; Bivalvia; Gene Flow; Genetic Introgression; Introduced Species; RNA, Long Noncoding; Transcriptome
PubMed: 33251632
DOI: 10.1111/jeb.13746 -
Evolution; International Journal of... Jul 2020A growing number of empirical studies have quantified the degree to which evolution is geometrically parallel by estimating and interpreting pairwise angles between...
A growing number of empirical studies have quantified the degree to which evolution is geometrically parallel by estimating and interpreting pairwise angles between multiple replicate lineages' evolutionary change vectors in multivariate trait space. Similar comparisons, of distance in trait space, are used to assess the degree of convergence. These approaches amount to element-by-element interpretation of distance matrices, typically testing for differences among replicate evolutionary vectors, compared to a null hypothesis of perfect parallelism. We suggest a complimentary set of approaches, co-opted from evolutionary quantitative genetics, involving eigen analysis and comparison of among-lineage covariance matrices. Such approaches allow one to identify multiple major axes of evolutionary change (e.g., alternative adaptive solutions), and also allow for the definition of biologically tenable null hypotheses, such as drift, against which empirical patterns can be tested. Reanalysis of a dataset of multivariate evolution across a replicated lake/stream gradient in threespine stickleback reveals that most of the variation in the direction of evolutionary change can be captured in just a few dimensions, indicating a greater extent of parallelism than previously appreciated. We suggest that applying such multivariate approaches may often be necessary to fully understand the extent and form of parallel and convergent evolution.
Topics: Adaptation, Biological; Animals; Biological Evolution; Models, Genetic; Multivariate Analysis; Smegmamorpha
PubMed: 32515132
DOI: 10.1111/evo.14035 -
Gastroenterology Report 2024Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice... (Review)
Review
Inflammatory bowel disease (IBD) research often relies on animal models to study the etiology, pathophysiology, and management of IBD. Among these models, rats and mice are frequently employed due to their practicality and genetic manipulability. However, for studies aiming to closely mimic human pathology, non-human primates such as monkeys and dogs offer valuable physiological parallels. Guinea pigs, while less commonly used, present unique advantages for investigating the intricate interplay between neurological and immunological factors in IBD. Additionally, New Zealand rabbits excel in endoscopic biopsy techniques, providing insights into mucosal inflammation and healing processes. Pigs, with their physiological similarities to humans, serve as ideal models for exploring the complex relationships between nutrition, metabolism, and immunity in IBD. Beyond mammals, non-mammalian organisms including zebrafish, , and nematodes offer specialized insights into specific aspects of IBD pathology, highlighting the diverse array of model systems available for advancing our understanding of this multifaceted disease. In this review, we conduct a thorough analysis of various animal models employed in IBD research, detailing their applications and essential experimental parameters. These include clinical observation, Disease Activity Index score, pathological assessment, intestinal barrier integrity, fibrosis, inflammatory markers, intestinal microbiome, and other critical parameters that are crucial for evaluating modeling success and drug efficacy in experimental mammalian studies. Overall, this review will serve as a valuable resource for researchers in the field of IBD, offering insights into the diverse array of animal models available and their respective applications in studying IBD.
PubMed: 38634007
DOI: 10.1093/gastro/goae021 -
Journal of Orthopaedic Science :... May 2018The association of scaphoid or other carpal bone fractures with distal radius fractures is frequently reported, whereas few studies have described pisiform malalignment...
BACKGROUND
The association of scaphoid or other carpal bone fractures with distal radius fractures is frequently reported, whereas few studies have described pisiform malalignment associated with distal radius fractures. The purpose of this study was to investigate the frequency and characteristics of pisiform malalignment associated with distal radius fractures.
METHODS
We performed a retrospective study by reviewing the data of 152 consecutive patients with a mean age of 63 years who were treated surgically for distal radius fractures during a five-year period. We evaluated the pisotriquetral joint via preoperative sagittal computed tomography (CT) and assessed pisiform malalignment. Pisiform malalignment was defined as follows: (1) wide type, joint space ≥4.0 mm; (2) non-parallel type, loss of parallelism of the joint surface of ≥20°; or (3) overriding type, proximal or distal overriding of the pisotriquetral joint ≥2.0 mm. We investigated the relationship between pisiform malalignment and the patterns of distal radius fractures. Pisiform malalignment was assessed using postoperative CT to determine whether it had been reduced.
RESULTS
Pisiform malalignment was observed in 48 cases involving 44 patients with a mean age of 58 (17-81) years. The patients included 16, 17, and 15 cases of the wide type, non-parallel type, and overriding type, respectively. Distal radius fractures with dorsal displacement exhibited pisiform malalignment significantly more frequently than those with volar displacement. No significant difference was noted between intra- and extra-articular fractures or between patients with and without distal ulnar fractures. Among the 22 pisiform malalignment cases assessed via postoperative CT, 15 cases were reduced, and 7 cases remained malaligned. The non-parallel type exhibited the lowest reduction rate among the 3 types.
CONCLUSIONS
Among distal radius fractures, 29% were complicated by pisiform malalignment. Distal radius fractures with dorsal displacement exhibited a significantly increased frequency of pisiform malalignment compared to those with volar displacement.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bone Malalignment; Female; Humans; Incidence; Intra-Articular Fractures; Male; Middle Aged; Pisiform Bone; Radius Fractures; Reproducibility of Results; Retrospective Studies; Risk Factors; Tomography, X-Ray Computed; Young Adult
PubMed: 29503035
DOI: 10.1016/j.jos.2018.02.010 -
Molecular Biology and Evolution Sep 2020Understanding the genetic basis of similar phenotypes shared between lineages is a long-lasting research interest. Even though animal evolution offers many examples of...
Understanding the genetic basis of similar phenotypes shared between lineages is a long-lasting research interest. Even though animal evolution offers many examples of parallelism, for many phenotypes little is known about the underlying genes and mutations. We here use a combination of whole-genome sequencing, expression analyses, and comparative genomics to study the parallel genetic origin of ptilopody (Pti) in chicken. Ptilopody (or foot feathering) is a polygenic trait that can be observed in domesticated and wild avian species and is characterized by the partial or complete development of feathers on the ankle and feet. In domesticated birds, ptilopody is easily selected to fixation, though extensive variation in the type and level of feather development is often observed. By means of a genome-wide association analysis, we identified two genomic regions associated with ptilopody. At one of the loci, we identified a 17-kb deletion affecting PITX1 expression, a gene known to encode a transcription regulator of hindlimb identity and development. Similarly to pigeon, at the second loci, we observed ectopic expression of TBX5, a gene involved in forelimb identity and a key determinant of foot feather development. We also observed that the trait evolved only once as foot-feathered birds share the same haplotype upstream TBX5. Our findings indicate that in chicken and pigeon ptilopody is determined by the same set of genes that affect similar molecular pathways. Our study confirms that ptilopody has evolved through parallel evolution in chicken and pigeon.
Topics: Animals; Biological Evolution; Chickens; Columbidae; Feathers; Foot; Haplotypes; Multifactorial Inheritance; Paired Box Transcription Factors; T-Box Domain Proteins; Whole Genome Sequencing
PubMed: 32344429
DOI: 10.1093/molbev/msaa092