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PubMed2026

Looking to the Future: How Will Personalised Medicine Impact Facial Plastic Surgery.

AIMS AND BACKGROUNDS: The objectives of this study are to examine the emerging role of personalized medicine in facial plastic surgery and to consider how biologically, anatomically, and psychologically tailored approaches may refine both aesthetic and reconstructive care. HISTORICAL ASPECTS: Facial plastic surgery has traditionally relied on anatomical principles, surgical expertise, and population-based evidence. Personalized medicine represents a shift toward more individualized care by incorporating patient-specific biological and phenotypic variation into clinical decision-making. ANATOMY: Facial plastic surgery is uniquely dependent on subtle anatomical variation, soft tissue characteristics, wound healing behavior, and age-related change. These factors differ considerably between individuals and have a direct impact on both surgical planning and outcomes. TECHNOLOGY: Advances in genomics, pharmacogenomics, artificial intelligence, tissue engineering, and three-dimensional modelling are expanding the scope of personalized care. These technologies may improve prediction of healing, treatment response, complication risk, and reconstructive requirements. PATIENT SELECTION: Personalized medicine may support more accurate patient selection by identifying those at increased risk of adverse scarring, variable response to injectables or pharmacotherapy, or differential reconstructive needs, thereby improving counselling and expectation management. TECHNIQUES: Potential applications include tailored incision planning, individualized facial rejuvenation strategies, personalized perioperative pharmacological regimens, and patient-specific reconstructive scaffolds, grafts, and implants. POSTOPERATIVE CARE: Postoperative management may also become more individualized through better prediction of inflammatory response, scar formation, analgesic requirements, and recovery trajectory, allowing more precise surveillance and adjunctive treatment. CURRENT AND FUTURE DEVELOPMENT: Although many applications remain investigational, continued progress in regenerative medicine, molecular profiling, and predictive analytics is likely to accelerate clinical translation. Ethical challenges relating to privacy, bias, and equitable access must, however, remain central. CONCLUSION AND CLINICAL RELEVANCE: Personalized medicine has the potential to enhance precision, safety, and patient-centered care in facial plastic surgery. Its future value will depend on thoughtful integration into practice as an adjunct to, rather than a replacement for, surgical judgement and aesthetic insight.

Journal Article↗

PubMed1998

Artificial chaperone-assisted refolding of citrate synthase.

The power of genetic engineering methods, along with increasing genomic information, makes heterologous expression of proteins an extremely important biochemical tool. Unfortunately, proteins obtained in this way often are not in their native form, and folding becomes a crucial step in protein production. We have recently developed a strategy that promotes the folding of chemically denatured proteins via the sequential addition of low molecular weight "artificial chaperones." Here we describe in detail the application of this method to porcine heart citrate synthase. Refolding yields of as high as 65% have been achieved. Mechanistic studies indicate that there are significant differences between artificial chaperone-assisted refolding of citrate synthase and artificial chaperone-assisted refolding of two other proteins that have been examined, carbonic anhydrase B (Rozema, D., and Gellman, S. H. (1996) J. Biol. Chem. 271, 3478-3487) and lysozyme (Rozema, D., and Gellman, S. H. (1996) Biochemistry 35, 15760-15771). The differences among these three test proteins reveal the range of procedural variation that must be considered in the application of the artificial chaperone method to new proteins.

Animals↗

PubMedDate not supplied

Strategic importance of research support through pathology.

The pace at which new drug candidates are being identified by Discovery Research demands that they be screened for preclinical attributes rapidly and efficiently. The early identification and elimination of compounds with toxic liabilities will produce safer drugs in a shorter time period, and with an increased rate of success. Most major pharmaceutical companies now recognize the strategic role of pathology support for research and have developed specific units to effect this outcome. The early interaction of these pathologists with drug discovery teams to identify compounds with toxic liabilities is critical. Approaches being used include high throughput in vitro screens to predict the relative toxicity of discovery compounds and to provide early indications of underlying mechanisms, target profiling to predict consequences of receptor-ligand interactions at other-than-indicated target sites, and acute in vivo studies to establish tolerability limits and target organs of toxicity. These approaches include the application of contemporary tools such as genomics, proteomics, metabonomics, and genetically engineered animal models. To maximize the benefit of discovery pathology, it is critical that pharmaceutical companies also actively participate in non-proprietary knowledge sharing and the education of pathologists and toxicologists to lead these efforts in the future.

Humans↗

PubMed1992

Structural and functional analysis of three D/L-like class I molecules from H-2v: indications of an ancestral family of D/L genes.

Three cDNA with D region gene features have been identified from the H-2v haplotype. Provisionally, the sequences have been designated as D/Lv1, D/Lv2, and D/Lv3. The coding segments for the antigen binding domain (ABD) of all three D/Lv genes were engineered into a class I genomic expression vector and expressed in L cells. FACS analysis of the three D/Lv-Ld gene transfectants revealed that the D/Lv1 molecules were recognized by both monoclonal antibodies (mAbs) 141 and 142, and the D/Lv2 molecules were recognized by mAb 143. In addition to the D/Lv1 molecules, the mAb 141 also recognized the D/Lv3 molecules. Both the D/Lv1-Ld and D/Lv2-Ld transfectants were killed efficiently by H-2Dv region-specific alloreactive CTL. The D/Lv3 gene is the first identified D region gene other than D and L that is transcribed abundantly in spleen and the D/Lv3 RNA is present as two alternatively spliced forms. Structural analysis of the D/Lv3 hybrid molecules showed that it was susceptible to proteolysis and thermolabile at 37 degrees C, suggesting D/Lv3 is a transcribed pseudogene. A parsimony tree analysis of three D/Lv sequences with a set of class I gene sequences revealed that the H-2v sequences clustered with D region genes. The presence of a third gene with D/L-like features in H-2v, yet structurally different from the known D/L alleles, raises the possibility that the current D/L genes evolved from a family of D/L-like genes, some of which are no longer represented among many of the mouse major histocompatibility complex haplotypes. The observation that D region alleles cluster into subgroups suggests that the alleles are not all related to each other by linear descent through a single locus. We propose that current alleles are derived from more than one ancestral locus in a manner similar to the origin of the gamma 2 a immunoglobulin constant region alleles.

Alleles↗

PubMed2026

Agentomics: an agentic system that autonomously develops novel state-of-the-art solutions for biomedical machine learning tasks.

MOTIVATION: Extracting knowledge from biomedical data is crucial for advancing our understanding of biological systems and developing novel therapeutics. The quantity, quality, and resolution of biomedical data constantly evolves, requiring the automation of biomedical machine learning (ML). Existing Automated ML tools lack flexibility, while large language models (LLMs) struggle to consistently deliver reproducible machine learning codebases, and existing LLM Agent-powered solutions lag behind human-engineered ML models. RESULTS: Here, we introduce Agentomics, an autonomous LLM-powered agentic system for end-to-end ML experimentation. Given a biomedical dataset, Agentomics implements various ML modeling strategies, and produces a ready-to-use ML model. Agentomics introduces strict validation checkpoints for standard ML development steps, allowing gradual development on top of working code with defined interfaces and validated artifacts. Further, it offers native support for biomedical foundation models that can be leveraged during experimentation. The generic nature of Agentomics allows the user to create ML solutions for a large variety of datasets and use various LLMs. We evaluate Agentomics across 20 datasets from the domains of Protein Engineering, Drug Discovery, and Regulatory Genomics. When benchmarked against other agentic systems, Agentomics outperformed them in all tested domains. When benchmarked against human expert solutions, Agentomics generated novel state-of-the-art models for 11/20 established benchmark datasets. AVAILABILITY AND IMPLEMENTATION: Agentomics is implemented in Python. Source code and documentation are freely available at: https://github.com/BioGeMT/Agentomics-ML.

Machine Learning↗

PubMed1995

Enhancer-trap targeting at the Broad-Complex locus of Drosophila melanogaster.

Here, we describe the exact replacement of a defective unmarked P element by an enhancer-trap transposon marked by the miniwhite gene and carrying lacZ as a reporter gene. The original defective P element was located in an intron of the Broad-Complex (BRC), a key gene involved in metamorphosis. Replacement events resulted from conversions induced by the P-element transposase from a donor enhancer-trap element located on another chromosome. Six independent conversion events were selected. In all converted chromosomes, the enhancer-trap transposon was in the same orientation as the original P element. From the pattern of X-gal staining observed, lacZ expression likely reflects the regulatory influence of BRC enhancers on the convertant transposon. Reversion to wild type was achieved by excision of the enhancer-trap transposon. The six convertants were analyzed in detail at the nucleotide level. The occurrence of a polymorphism at position 33 of the P-element sequences led us to propose a conversion mechanism involving homologous P sequences for repair. This is in contrast to previously analyzed P-element transposase-induced conversion events and proposed models relying on sequence identity between genomic Drosophila sequences. The lack of any homology requirement other than between P element sequences means that our findings can be easily generalized. Targeting a marked P-element derivative at a precise site without loss or addition of genetic information makes it possible to exploit the hundreds of defective P elements scattered throughout the Drosophila genome by replacing them with engineered P elements, already available.

Animals↗

PubMed1999

Reovirus virion-like particles obtained by recoating infectious subvirion particles with baculovirus-expressed sigma3 protein: an approach for analyzing sigma3 functions during virus entry.

Structure-function studies with mammalian reoviruses have been limited by the lack of a reverse-genetic system for engineering mutations into the viral genome. To circumvent this limitation in a partial way for the major outer-capsid protein sigma3, we obtained in vitro assembly of large numbers of virion-like particles by binding baculovirus-expressed sigma3 protein to infectious subvirion particles (ISVPs) that lack sigma3. A level of sigma3 binding approaching 100% of that in native virions was routinely achieved. The sigma3 coat in these recoated ISVPs (rcISVPs) appeared very similar to that in virions by electron microscopy and three-dimensional image reconstruction. rcISVPs retained full infectivity in murine L cells, allowing their use to study sigma3 functions in virus entry. Upon infection, rcISVPs behaved identically to virions in showing an extended lag phase prior to exponential growth and in being inhibited from entering cells by either the weak base NH4Cl or the cysteine proteinase inhibitor E-64. rcISVPs also mimicked virions in being incapable of in vitro activation to mediate lysis of erythrocytes and transcription of the viral mRNAs. Last, rcISVPs behaved like virions in showing minor loss of infectivity at 52 degrees C. Since rcISVPs contain virion-like levels of sigma3 but contain outer-capsid protein mu1/mu1C mostly cleaved at the delta-phi junction as in ISVPs, the fact that rcISVPs behaved like virions (and not ISVPs) in all of the assays that we performed suggests that sigma3, and not the delta-phi cleavage of mu1/mu1C, determines the observed differences in behavior between virions and ISVPs. To demonstrate the applicability of rcISVPs for genetic studies of protein functions in reovirus entry (an approach that we call recoating genetics), we used chimeric sigma3 proteins to localize the primary determinants of a strain-dependent difference in sigma3 cleavage rate to a carboxy-terminal region of the ISVP-bound protein.

Animals↗

PubMed2000

Mengovirus and encephalomyocarditis virus poly(C) tract lengths can affect virus growth in murine cell culture.

Many virulent aphthoviruses and cardioviruses have long homopolymeric poly(C) tracts in the 5' untranslated regions of their RNA genomes. A panel of genetically engineered mengo-type cardioviruses has been described which contain a variety of different poly(C) tract lengths. Studies of these viruses have shown the poly(C) tract to be dispensable for growth in HeLa cells, although the relative murine virulence of the viruses correlates directly and positively with tract length. Compared with wild-type mengovirus strain M, mutants with shortened poly(C) tracts grow poorly in mice and protectively immunize rather than kill recipient animals. In the present study, several murine cell populations were tested to determine whether, unlike HeLa cells, they allowed a differential amplification of viruses with long or short poly(C) tracts. Replication and cytopathic studies with four hematopoietically derived cell lines (CH2B, RAW 264.7, A20.J, and P815) and two murine fibroblast cell lines [L929 and L(Y)] demonstrated that several of these cell types indeed allowed differential virus replication as a function of viral poly(C) tract length. Among the most discerning of these cells, RAW 264.7 macrophages supported vigorous lytic growth of a long-tract virus, vMwt (C(44)UC(10)), but supported only substantially diminished and virtually nonlytic growth of vMC(24) (C(13)UC(10)) and vMC(0) short-tract viruses. The viral growth differences evident in all cell lines were apparent early and continuously during every cycle of virus amplification. The data suggest that poly(C) tract-dependent attenuation of mengovirus may be due in part to a viral replication defect manifest in similar hematopoietic-type cells shortly after murine infection. The characterized cultures should provide excellent tools for molecular study of poly(C) tract-mediated virulence.

Animals↗

PubMed2000

Remodeling the cardiac sarcomere using transgenesis.

An underpinning of basic physiology and clinical medicine is that specific protein complements underlie cell and organ function. In the heart, contractile protein changes correlating with functional alterations occur during both normal development and the development of numerous pathologies. What has been lacking for the majority of these observations is an extension of correlation to causative proof. More specifically, different congenital heart diseases are characterized by shifts in the motor proteins, and the genetic etiologies of a number of different dilated and hypertrophic cardiomyopathies have been established as residing at loci encoding the contractile proteins. To establish cause, or to understand development of the pathophysiology over an animal's life span, it is necessary to direct the heart to synthesize, in the absence of other pleiotropic changes, the candidate protein. Subsequently one can determine whether or how the protein's presence causes the effects either directly or indirectly. By affecting the heart's protein complement in a defined manner, the potential to establish the function of different proteins and protein isoforms exists. Transgenesis provides a means of stably modifying the mammalian genome. By directing expression of engineered proteins to the heart, cardiac contractile protein profiles can be effectively remodeled and the resultant animal used to study the consequences of a single, genetic manipulation at the molecular, biochemical, cytological, and physiological levels.

Animals↗

PubMed2025

Algorithms to reconstruct past indels: The deletion-only parsimony problem.

Ancestral sequence reconstruction is an important task in bioinformatics, with applications ranging from protein engineering to the study of genome evolution. When sequences can only undergo substitutions, optimal reconstructions can be efficiently computed using well-known algorithms. However, accounting for indels in ancestral reconstructions is much harder. First, for biologically-relevant problem formulations, no polynomial-time exact algorithms are available. Second, multiple reconstructions are often equally parsimonious or likely, making it crucial to correctly display uncertainty in the results. Here, we consider a parsimony approach where only deletions are allowed, while addressing the aforementioned limitations. First, we describe an exact algorithm to obtain all the optimal solutions. The algorithm runs in polynomial time if only one solution is sought. Second, we show that all possible optimal reconstructions for a fixed node can be represented using a graph computable in polynomial time. While previous studies have proposed graph-based representations of ancestral reconstructions, this result is the first to offer a solid mathematical justification for this approach. Finally we provide arguments for the relevance of the deletion-only case for the general case.

Algorithms↗

PubMed2026

A Comprehensive Review on the Biosynthesis of Tropane Alkaloids.

Tropane alkaloids (TA) constitute a class of plant specialized metabolites with important pharmaceutical applications, including the anticholinergic agents hyoscyamine and scopolamine and the local anesthetic cocaine. Over the past decade, advances in genomics, structural biology, and synthetic biology have substantially revised our understanding of TA biosynthesis, leading to the identification of numerous key biosynthetic enzymes and evolutionary mechanisms. This review comprehensively summarizes current knowledge of TA biosynthesis from precursor formation to structurally diverse end products. We describe the pathway from putrescine to tropinone, the stereoselective metabolic branching mediated by Tropinone Reductases, and the downstream biosynthesis of medicinal tropane alkaloids, calystegines, and cocaine. Particular emphasis is placed on recent discoveries concerning catalytic mechanisms, structural determinants of substrate specificity, metabolic compartmentalization, and the convergent evolution of TA biosynthesis in Solanaceae and Erythroxylaceae. We further integrate advances in genomics, evolutionary biology, and metabolic engineering to highlight emerging strategies for microbial production and pathway redesign. By providing a comprehensive synthesis of recent progress and critical perspectives on unresolved questions, this review offers an updated framework for understanding TA biosynthesis and supports future research in plant specialized metabolism, synthetic biology, and natural product engineering.

Tropanes↗

PubMedDate not supplied

[Gene therapy for the treatment of patients with brain gliomas].

The prognosis of patients with brain gliomas remains poor despite the use of advanced surgical techniques, radio- and chemotherapy. In this respect, gene engineering techniques altering the glioma genome in order to regulate the function of key genes involved in cancerogenesis seem to be promising. The premise for applying a gene therapy in patients with brain gliomas is described, together with basic strategies and results of hitherto performed experimental and clinical studies, mostly with the use of virus vectors. The rapid progress in molecular techniques may enable to overcome methodological problems related to the introduction of the therapeutic gene into the target cell, and thus to improve so far unsatisfactory results of glioma gene therapy. The important role of a neurosurgeon in the process of precise gene vector application to the tumour area should not be underestimated.

Apoptosis Regulatory Proteins↗

PubMed1989

[Limits and risks of biotechnology in veterinary medicine from the viewpoint of the reproductive biologist].

New biotechnical methods in reproduction have been introduced in animal breeding via embryo transfer. There are no serious objections against these methods as long as the variety of species is reassured and the animal protection law is considered. More substantial objections exist against genetic engineering methods which alter the genome of animals. Beside for legal protection there is a strong public demand for the adequete awareness and responsibility of scientists who are active in this field. Comprehensive information on such research projects can lead to a better understanding of the aims and methods and might, therefore, help to reduce inadequate apprehensions.

Animals↗

PubMed2026

Mechanistic Perspectives From Genomics and Pangenomics of Medicinal and Aromatic Plants: Linking Genome Architecture to Phytochemical Diversity.

Medicinal and aromatic plants (MAPs) produce a remarkable diversity of specialized metabolites with significant pharmaceutical, nutraceutical, and industrial value. Although advances in long-read sequencing, chromosome-scale genome assembly, and pangenomics have greatly expanded genomic resources, the mechanistic links between genome architecture and phytochemical diversity remain incompletely understood. The present review synthesizes current evidence describing how structural genomic variation may contribute to phytochemical diversity, while acknowledging that many proposed genome-to-metabolite relationships require further experimental validation. Examples illustrate how genome architecture is associated with specialized-metabolite biosynthesis through multiple regulatory processes. However, the strength of supporting evidence varies considerably among MAP species. Moreover, relatively few genome-to-metabolite relationships have been confirmed through direct functional validation. We further discuss how pangenomics, multiomics integration, genome editing, synthetic biology, and artificial intelligence support the discovery, validation, and engineering of specialized metabolic pathways. Casual conclusions are evaluated according to the strength of available evidence, highlighting where causal relationships have been experimentally established and where conclusions remain primarily association-based. Overall, this review provides an integrated conceptual and evidence-based perspective summarizing proposed relationships between genome architecture and phytochemical diversity and outlines future priorities for functional genomics, precision breeding, metabolic engineering, and sustainable utilization of MAPs.

artificial intelligence↗

PubMed2001

Advances in sequence analysis.

In its early days, the entire field of computational biology revolved almost entirely around biological sequence analysis. Over the past few years, however, a number of new non-sequence-based areas of investigation have become mainstream, from the analysis of gene expression data from microarrays, to whole-genome association discovery, and to the reverse engineering of gene regulatory pathways. Nonetheless, with the completion of private and public efforts to map the human genome, as well as those of other organisms, sequence data continue to be a veritable mother lode of valuable biological information that can be mined in a variety of contexts. Furthermore, the integration of sequence data with a variety of alternative information is providing valuable and fundamentally new insight into biological processes, as well as an array of new computational methodologies for the analysis of biological data.

Computational Biology↗

PubMed1995

An efficient procedure to select and recover recombinant adenovirus vectors.

Adenoviruses are efficient gene transfer vectors for a variety of cell types. To date, the most widely used methods to construct recombinant adenoviruses involve either in vitro ligation or recombination between one-half of the virus genome, previously cloned in a plasmid vector and engineered to contain the desired expression cassette, and the other half of the virus genome prepared from virions. Although quite effective, these approaches produce viral progeny containing a mixture of recombinant and parental background virus. Thus the recovery of the recombinant virus can be difficult, especially when it grows more slowly than the parental virus. To improve selection and recovery of recombinant adenoviruses, we have constructed an adenovirus vector, AdTG6553, in which the E1 region has been replaced by the thymidine kinase (tk) gene of herpes simplex virus type 1. We show that infection of cells with AdTG6553 in the presence of the nucleoside analog ganciclovir (GCV) prevents viral replication. The conditional lethal phenotype introduced in AdTG6553 makes it a valuable tool to counter-select parental background virus in the presence of GCV and isolate replication-deficient recombinant adenoviruses in which the tk expression cassette has been replaced by a new gene.

Adenoviridae↗

PubMedDate not supplied

[Bioethics in genetic engineering].

The advances in the field of molecular biology and genetics have widened the possibilities for the diagnosis and treatment of hereditary diseases. At the same time research into this field has broken bounds of its legal and ethical regulation. The intention of this paper is not to analyze these advances from scientific and technical point of view which is the area of the specialist, but rather to review historical antecedents of genetic engineering; the legal and ethical repercussions of the human genome project (HGP); in vitro fertilization and embryo transfer (FIVET); the embryo research which is being caused out and which may be possible; other fields of genetics and cloning especially germinal cells and human beings; genetic diagnosis and its family, social and work repercussions; treatment through genetic engineering, research into cloning in order to obtain organs and tissues for transplants; and the use of genetic engineering in the biomedical industry. To avoid these advances working against humans, the organization and participation of multidisciplinary bodies are required to provide legal and ethical supervision.

Bioethical Issues↗

PubMed2004

The relevance of genetic analysis to dairy bacteria: building upon our heritage.

Lactic acid bacteria (LAB) are essential for the manufacture of fermented dairy products. Studies on the physiology, biochemistry and genetics of these microorganisms over the last century have contributed considerably to the improvement of fermentation processes and have resulted in better and safer products. Nevertheless, the potential of LAB is far from being maximized. The sophistication of biotechnologies and the availability of complete genome sequences have opened the door to the metabolic engineering of LAB. In this regard, the recent publication of the complete genome sequences of two Streptococcus thermophilus strains will provide a key tool to facilitate the genetic manipulation of this important dairy species.

Editorial↗