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PubMed2026

TFAM organizes DNA into compact higher order structures.

TFAM (Transcription Factor A, Mitochondrial) is an essential human protein that plays two key roles in mitochondrial DNA (mtDNA) homeostasis. TFAM acts as a transcription factor that specifically binds to promoter regions, but it is also solely responsible for organizing mtDNA into nucleoids by nonspecifically covering the entire genome. Many studies have addressed TFAM in transcription regulation, but its role as a genome organizing entity is not well characterized. The current understanding of how TFAM compacts DNA into nucleoids is based on crystal structures of a TFAM monomer bound to short fragments of DNA (22-28 bp). However, this does not adequately reflect the biological role of TFAM in organizing the nucleoid where multiple TFAM molecules oligomerize on the 16.5 kb genome to form the nucleoid. Here, we present a biochemical and structural analysis of TFAM oligomerization on longer DNA. Our results show that TFAM compacts longer segments of DNA into higher order complexes that are homogenous yet exhibit continuous conformational dynamics.

Major classification: Biological sciences↗

PubMed1995

Electronic surveillance of the pharmacology-toxicology literature: the need for controlled vocabularies and registry systems.

Controlled vocabularies of "preferred names" and registry systems are essential in electronic indexing, storing, searching, and retrieving the world's published literature. The most efficient and comprehensive search is accomplished by using the preferred name. Without a controlled vocabulary or a registry system, it would be necessary to remember every name that might have been used by authors since January 1966, in order to retrieve all the citations on a chemical from over 7.8 million citations currently in the National Library of Medicine's MEDLINE and its backfiles. The task of creating the list of subject descriptors that make possible the surveillance of published literature via electronic databases requires the participation of the scientific community in developing domain-specific nomenclature, drug classification, controlled vocabularies, and registry systems as well. The biological unions of the International Council of Scientific Unions and its Committee on Data for Science and Technology are major contributors to the establishment and dissemination of standards for biological terminology and nomenclature. The objectives of the IUPHAR Nomenclature Committee include the development of a rational framework for the nomenclature of receptor classes or families and a classification for therapeutic agents. This will help define rules for the characterization and classification of receptors that are stable and easy to comprehend. The International Union of Pharmacology publishes guidelines for the classification of drugs and the nomenclature of receptors and ion channels.

Abstracting and Indexing↗

PubMed1987

History of not completing courses as predictor of academic difficulty among first-year students.

The study reported here was undertaken to determine whether the prediction of academic difficulty in the first year of medical school is enhanced by a consideration of the number of courses withdrawn from, repeated courses, and incomplete courses on a student's undergraduate academic record. All students enrolled from 1981 through 1985 at Southern Illinois University School of Medicine who experienced academic difficulty in the first year were selected for the study. Successful students were matched with these students in terms of minority or majority status and served as a control group. Discriminant and classification analyses were performed in a hierarchical stepwise manner to predict success or difficulty in the first year. The variables that were significant in discriminating between minority students who had academic difficulty and those who did not were the science grade-point average (grades in biology, chemistry, physics, and mathematics), the score on the reading subtest of the Medical College Admission Test (MCAT), and the number of withdrawals from courses. For majority students, the significant discriminating variables were the score on the MCAT biology subtest and the number of incompletes taken for courses. The results of this study have implications for medical school admissions committees, premedical advisers, and premedical students.

Education, Medical, Undergraduate↗

PubMed1998

Recommendations for the registration of drugs used in the treatment of rheumatoid arthritis. Group for the Respect of Ethics and Excellence in Science (GREES): rheumatoid arthritis section.

Rheumatoid arthritis (RA) is the commonest form of chronic inflammatory joint disease and a major target for symptom-modifying and disease-modifying drug therapy. New approaches to the treatment of RA using biological agents targeted to cellular receptors, cytokines and other mediators of inflammation, together with the availability of new methods of outcome assessment, make it timely to reconsider the classification of anti-rheumatic drugs and the requirements for the registration of new drug entities. Under the auspices of GREES (Group for the Respect of Ethics and Excellence in Science), a European Working Group of clinicians with experience in rheumatology, scientists and representatives from industry and national drug licensing authorities have formulated recommendations for the requirements for registration of anti-rheumatic drugs designed for symptom modification, structural modification and the suppression of inflammation, with particular emphasis placed on quality of life assessment by generic and disease-specific validated methods. This paper outlines the group's advice for pre-clinical testing, and Phase I, Phase II and Phase III trials to allow licences to be granted for each indication, while recognizing that a single drug may have reason to be approved under several headings.

Antirheumatic Agents↗

PubMed2000

Computational tools for protein modeling.

Protein modeling is playing a more and more important role in protein and peptide sciences due to improvements in modeling methods, advances in computer technology, and the huge amount of biological data becoming available. Modeling tools can often predict the structure and shed some light on the function and its underlying mechanism. They can also provide insight to design experiments and suggest possible leads for drug design. This review attempts to provide a comprehensive introduction to major computer programs, especially on-line servers, for protein modeling. The review covers the following aspects: (1) protein sequence comparison, including sequence alignment/search, sequence-based protein family classification, domain parsing, and phylogenetic classification; (2) sequence annotation, including annotation/prediction of hydrophobic profiles, transmembrane regions, active sites, signaling sites, and secondary structures; (3) protein structure analysis, including visualization, geometry analysis, structure comparison/classification, dynamics, and electrostatics; (4) three-dimensional structure prediction, including homology modeling, fold recognition using threading, ab initio prediction, and docking. We will address what a user can expect from the computer tools in terms of their strengths and limitations. We will also discuss the major challenges and the future trends in the field. A collection of the links of tools can be found at http://compbio.ornl.gov/structure/resource/.

Algorithms↗

PubMed2025

Algorithms and tools for data-driven omics integration to achieve multilayer biological insights: a narrative review.

Systems biology is a holistic approach to biological sciences that combines experimental and computational strategies, aimed at integrating information from different scales of biological processes to unravel pathophysiological mechanisms and behaviours. In this scenario, high-throughput technologies have been playing a major role in providing huge amounts of omics data, whose integration would offer unprecedented possibilities in gaining insights on diseases and identifying potential biomarkers. In the present review, we focus on strategies that have been applied in literature to integrate genomics, transcriptomics, proteomics, and metabolomics in the year range 2018-2024. Integration approaches were divided into three main categories: statistical-based approaches, multivariate methods, and machine learning/artificial intelligence techniques. Among them, statistical approaches (mainly based on correlation) were the ones with a slightly higher prevalence, followed by multivariate approaches, and machine learning techniques. Integrating multiple biological layers has shown great potential in uncovering molecular mechanisms, identifying putative biomarkers, and aid classification, most of the time resulting in better performances when compared to single omics analyses. However, significant challenges remain. The high-throughput nature of omics platforms introduces issues such as variable data quality, missing values, collinearity, and dimensionality. These challenges further increase when combining multiple omics datasets, as the complexity and heterogeneity of the data increase with integration. We report different strategies that have been found in literature to cope with these challenges, but some open issues still remain and should be addressed to disclose the full potential of omics integration.

Algorithms↗

PubMed1982

Analytical goals and the College of American Pathologists.

Classifications of measurement procedures rank routine control and laboratory simulation as the most difficult measurements. Their use in laboratory medicine has led to the development of a science whose purpose is to quantitate various characteristics of laboratory performance. The College of American Pathologists application of the science takes the form of its quality assurance programs, notably the Survey Programs. Until recently, however, the concern for reduction of analytical error and the engrafted aspects of regulation have diverted attention from the major purpose of the programs: the establishment and achievement of analytical goals based on clinical utility. The College is working toward these ends, and its work is based on the following principles: (1) formulation of analytical goals is the responsibility of the profession; (2) the analytical goals are a scientific composite of total analytical error, biologic variation, and medical judgement; (3) analytical goals must be adjustable to accommodate laboratory and clinical advances.

Data Collection↗

PubMed2004

Stability or stasis in the names of organisms: the evolving codes of nomenclature.

Nomenclature, far from being a dry dusty subject, is today more relevant than ever before. Researchers into genomics are discovering again the need for systems of nomenclature-names are what we use to communicate about organisms, and by extension the rest of their biology. Here, we briefly outline the history of the published international codes of nomenclature, tracing them from the time of Linnaeus in the eighteenth century to the present day. We then outline some of what we feel are the major challenges that face the codes in the twenty-first century; focusing primarily on publication, priority, typification and the role of science in the naming of organisms. We conclude that the codes are essential for taxonomists in the pursuance of their science, and that the democratic nature of decision-making in the regulation of the rules of nomenclature, though sometimes perceived as a potential weakness, is in fact one of its great strengths.

Classification↗

PubMed2001

[Pathology and clinical medicine in the 21st Century].

The major task of pathology is to bridge the gap between basic science and clinical medicine. Consequently, pathology has to keep pace particularly with the progress in molecular biology and genetics and has to transfer the progress of basic research to studies of disease. Pathology has to test and continuously incorporate new methods into its scientific and diagnostic repertoire to improve diagnostic sensitivity and accuracy. The recognition of genetic alterations, particularly associated with tumors and chronic degenerative diseases, and its consequences in correlation with morphology allows the evaluation of changes in the genetic set-up and related cellular functions. This greatly improves the basis for understanding the biological background and clinical behavior of disease, thus adding a dynamic component to the snap-shot picture provided by the histologic slide. Application of genomics and proteomics will have significant impact on diagnostic pathology in the 21st century regarding definition and classification of pathologic processes, assessment of prognosis and guidance of treatment. The modern pathologist has to accept this challenge in order to maintain his position in the center of clinical medicine. However, despite all present and future advances, experience and skills in the morphologic evaluation of disease processes will still remain the "gold standard" in our field and the basis for proper application of these new technologies. When we accept the promising new techniques and tools already at the present early stage of development we may not only improve the clinical relevance of our work but gain invaluable information on the nature of diseases and the basic principles responsible for the complex morphologic pictures we enjoy in our daily work.

Clinical Medicine↗

PubMed2003

Criteria for classification of medical information.

Medical information, which is the central notion in medical informatics, covers a large scale of structures and forms. Several classifications are possible and two criteria have been used in this paper: structural level and informational level. According to structural level we can distinguish three major areas: bioinformatics and neuroinformatics for molecular/cellular level, medical informatics for individual level and health informatics for community level and healthcare units. According to informational level the terms of data and knowledge are used and the representative information for each structural level is analysed also from this point of view: Finally, information transfer from living systems to computers is also seen through the structural point of view.

Biological Science Disciplines↗

PubMed1997

Thyroid carcinoma.

During the past years advances have been made in the understanding of the molecular mechanisms involved in the initiation and progression of thyroid carcinoma. Mutations in tumor suppressor genes such as p53 and oncogenes such as N-ras may be important for progression of well-differentiated thyroid carcinomas. Activation of the ret protooncogene located on chromosomal region 10q11.2 has been identified as a key factor in the initiation of papillary and medullary carcinoma. Integration of these discoveries into a prognostic classification scheme may allow us to better predict the biologic behavior of tumors in individual patients. Despite the recent advances in our understanding of the molecular events occurring during thyroid carcinogenesis, major questions persist regarding aspects of patient management. New diagnostic modalities may enable us to noninvasively discriminate between benign and malignant thyroid nodules, and to detect recurrent disease earlier. Although the optimal surgical procedure for well-encapsulated tumors is still debated, recent clinical studies have shown that for those patients with tumors > 1.5 cm, the routine use of RAI and hormone suppression can improve local control and survival rates. Findings in two recent reviews suggest that patients with widely invasive thyroid masses benefit from the surgical removal of all gross tumor. Further investigation is required to define the role of adjuvant radiotherapy and the most appropriate management of unresectable disease. Incorporation of prognostic markers into clinical staging systems should allow surgeons to better tailor their treatment plans for each patient. Translation of recent basic science advances into the clinical arena may also aid in the development of novel treatment strategies for patients with aggressive tumors.

Carcinoma, Medullary↗

PubMed2000

Evaluation of traffic noise-related cardiovascular risk.

In this paper we discuss the risk of myocardial infarction induced by traffic noise within the conceptual framework for risk assessment suggested by the US National Research Council. The characterisation of cardiovascular risk is evaluated using a four-dimensional set of evaluation criteria: severity of health effect, frequency of exposures considered relevant for health, size of estimated risk, and validity of risk assessment. For quantification of risk we calculated lifetime risks using standard methods applied for quantitative cancer risk estimation. In evaluation of validity we refer to criteria that the International Agency for Research on Cancer has developed for classification of epidemiological evidence. Compared to other adverse effects regarded in regulatory toxicology, myocardial in-farction is a severe health effect. Assuming that sound pressure levels Leq, 6-22 hr above 65 dB(A) are associated with an increased cardiovascular risk, a major portion of the German population (about 16 %) is exposed to health relevant noise levels. Estimated lifetime risk amounts to 20:1,000 and exceeds considerably the lifetime risk induced by other environmental hazards or tolerable risk levels suggested in other contexts. A causal association between noise exposure and infarction risk, however, cannot be taken as proven scientifically, because chance, bias or con-founding cannot be ruled out with reasonable confidence. Methodological quality of the studies performed, consistency of findings, dose-response relations, coherence with a recent occupational study and biological plausibility nevertheless support a causal interpretation. Thus, an integrative evaluation of all available information may justify the conclusion that a causal interrelationship is probable. The conclusions for regulation strongly depend on how the high risk potential is balanced against the uncertain causality assessment. This question cannot be answered by science but must be decided politically. From a public health perspective noise exposure should be reduced in order to protect human health.

Journal Article↗

PubMed2004

Regenerative medicine: stem cells and the science of monstrosity.

The nineteenth century science of teratology concerned itself with the study of malformations or "monstrosities", as they were then called. The first major contribution to the field was the work of Isidore Geoffrey Saint-Hilaire, Historie Generale et Particuliere des Anomalies de l'Organisation chez l'Homme et les Animaux, published in 1832, whose classifications formed the basis for the later experimental science of teratogeny, the art of reproducing monstrosities in animal embryos. In this article, I will argue that recent developments in the field of regenerative medicine can be situated in the tradition of teratological and teratogenic studies dating back to the nineteenth century. In particular, I will be interested in the historical link between studies in teratogenesis (the artificial production of teratomas) and stem cell research. Recent advances in stem cell research, I will suggest, return us to the questions that animated nineteenth century investigations into the nature of the monstrous or the anomalous. In the process, our most intuitive conceptions of "life itself" are undergoing a profound transformation.

Animals↗

PubMed1999

A comprehensive analysis of selected diagnostic methods with respect to their usefulness in evaluating the biology of neoplastic cells in patients with laryngeal cancer.

The difficult and complicated mechanism of cancer development with little knowledge about the biology of existing cancers can lead to a permanent search for new examination techniques to improve the precision of life expectancy in patients and the selection of the most efficient methods of treatment. The aim of this study was to analyze certain prognostic factors, i.e., p53, Ki67, proliferating cell nuclear antigen (PCNA), DNA ploidy and cell proliferating activity, as well as the degree of morphological differentiation and cell maturity evaluated on an ultrastructural level in patients with laryngeal cancers in connection with data obtained from follow-up examinations and the clinical course of the disease. Neoplastic tissue was taken from 120 patients with laryngeal cancers. All underwent surgical treatment, radiotherapy and combined treatment in the Department of Otolaryngology. Karol Marcinkowski University School of Medical Sciences, Poznań, Poland, and the Department of Otolaryngology-Head and Neck Surgery, Haukeland University, Bergen, Norway. Before beginning treatment all patients underwent histological verification of their neoplastic tissues. Histopathological examination proved that the majority of cases (95%) had a squamous cell carcinoma. The occurrence of changes within the lymph nodes of the neck (N) was significantly correlated with T, S, Ki67, metastases to lymph nodes, DNA ploidy, site and surgery performed. The degree of clinical progression (S) was intercorrelated with T, N, p53, Ki67, PCNA, DNA ploidy, site and laryngectomy. The occurrence of oncoprotein p53 in neoplastic cells was measured by the staining degree of their nuclei and was correlated with T, S, DNA ploidy, metastases to lymph nodes, PCNA and site. The degree of staining of neoplastic cells for the nuclear antigen Ki67 was correlated to T, N, G, S, DNA ploidy, metastases to lymph nodes and surgical treatment. The proliferative antigen PCNA in the examined population of patients was intercorrelated with T, p53, Ki67, metastases to lymph nodes and surgical treatment. The results obtained from DNA flow cytometry could be associated with N, G, p53, Ki67 and metastases to lymph nodes. On the basis of the results obtained, the techniques suggested for the morphological and biological evaluation of neoplastic cells in cancer of the larynx should include TNM classification + G + DNA + p53 + Ki67.

Adult↗

PubMed2026

Clinicopathological response and survival outcomes of HER2-low versus HER2-zero early breast Cancer: A systematic review and Meta-analysis.

BACKGROUND: Breast cancer is the most common malignant tumor in women. Human epidermal growth factor receptor 2 (HER2) is a key biomarker for classification and treatment. A subgroup with HER2-low expression has been identified, but existing evidence is heterogeneous. This systematic review and meta-analysis compared pathological response and survival outcomes between HER2-low and HER2-zero early-stage breast cancer to clarify prognostic features. METHODS: This study followed PRISMA guidelines and was registered in PROSPERO (CRD420251120506). PubMed, Embase, Web of Science, ClinicalTrials.gov, and major oncology conferences were searched through September 2025. Cohort studies of early-stage breast cancer comparing HER2-low (IHC 1+/2+ and ISH-negative) vs. HER2-zero with extractable pCR, DFS, or OS data were included. Studies involving HER2-positive patients or inconsistent definitions were excluded. Meta-analyses were performed using RevMan 5.3. RESULTS: Twenty-eight studies involving 115,182 patients were included. HER2-low patients showed significantly lower pCR rates (OR = 0.58, 95% CI: 0.52-0.65). DFS favored HER2-low (multivariate HR = 0.75, 95% CI: 0.69-0.83), especially in HR+ tumors, with a weaker effect in HR- cases. OS also favored HER2-low (HR = 0.80, 95% CI: 0.72-0.89), mainly driven by the HR- subgroup; no OS difference was seen in HR+ tumors. Sensitivity analyses and funnel plots indicated robust results with no apparent publication bias. Overall study quality was high (17 high-quality, 11 moderate-quality). CONCLUSION: HER2-low early breast cancer shows lower pCR after neoadjuvant therapy but better long-term survival. These findings support the clinical relevance of HER2-low as a biologically meaningful subgroup within HER2-negative disease, while its status as a stable and independent subtype still requires further validation through prospective studies, standardized testing, and multi-omics investigation.

Humans↗

PubMed2001

Role of genomic typing in taxonomy, evolutionary genetics, and microbial epidemiology.

Currently, genetic typing of microorganisms is widely used in several major fields of microbiological research. Taxonomy, research aimed at elucidation of evolutionary dynamics or phylogenetic relationships, population genetics of microorganisms, and microbial epidemiology all rely on genetic typing data for discrimination between genotypes. Apart from being an essential component of these fundamental sciences, microbial typing clearly affects several areas of applied microbiological research. The epidemiological investigation of outbreaks of infectious diseases and the measurement of genetic diversity in relation to relevant biological properties such as pathogenicity, drug resistance, and biodegradation capacities are obvious examples. The diversity among nucleic acid molecules provides the basic information for all fields described above. However, researchers in various disciplines tend to use different vocabularies, a wide variety of different experimental methods to monitor genetic variation, and sometimes widely differing modes of data processing and interpretation. The aim of the present review is to summarize the technological and fundamental concepts used in microbial taxonomy, evolutionary genetics, and epidemiology. Information on the nomenclature used in the different fields of research is provided, descriptions of the diverse genetic typing procedures are presented, and examples of both conceptual and technological research developments for Escherichia coli are included. Recommendations for unification of the different fields through standardization of laboratory techniques are made.

Bacteria↗

PubMed2026

Classification and sequencing of hepatitis D virus from a large cohort of chronically infected individuals paired with co-infecting hepatitis B virus sequencing: a genomic characterisation study.

BACKGROUND: The most severe form of viral hepatitis is caused by co-infection of hepatitis D virus (HDV) and hepatitis B virus (HBV). Phylogenetic analyses classify HBV and HDV into eight major genotypes: HBV GTA to GTH and HDV GT1 to GT8. Paired HBV and HDV sequencing data from participants with chronic hepatitis delta are scarce. We aimed to sequence and genotype HDV and HBV from a large cohort of participants from clinical studies and diverse countries of origin. METHODS: 407 participants with chronic hepatitis D from 24 countries were characterised (124 participants from MYR301 clinical trial, 93 from MYR204, 114 from MYR202, and an additional 76 participants from diverse geographical locations). HBV and HDV from participants were analysed using sequencing, enzyme immunoassay, or both to determine HBV and HDV genotypes. BLAST analysis and phylogenetics were used to determine HBV and HDV genotypes with reference sequence libraries. Bulevirtide treatment response (measured by HDV RNA decline and normalisation of alanine aminotransferase) was compared by genotype for MYR trial participants. FINDINGS: HDV sequencing assays were successful for 386 (95%) of 407 participants and HBV sequencing or serology-based HBV genotyping assays were successful for genotyping 395 (97%) participants. For individual genotypes, HBV GTD (336 [83%] participants) and HDV GT1 (364 [89%]) were the most prevalent. For paired HBV-HDV genotypes, HBV-HDV D/1 was most common (320 [79%] of 407) followed by A/1 (30 [7%]). Phylogenetic analyses of HDV full-genome sequences showed distinct clusters of sequences within HDV GT1, and four novel provisional HDV GT1 subgenotypes, HDV GT1fp to HDVGT1ip, were identified. For 218 MYR clinical trial participants, bulevirtide treatment response was similar across HDV GT1 subgenotypes (both established and newly identified). INTERPRETATION: Novel HDV subgenotypes identified in this study indicate a greater genetic diversity of HDV GT1 than previously recognised. This knowledge will be important for developing better diagnostics, and in understanding HDV genotype-specific biology and response to treatment. More extensive HDV sequencing from under-sampled regions, such as Africa, is needed to determine the true breadth of HDV sequence and genotype diversity. FUNDING: Gilead Sciences.

Hepatitis Delta Virus↗

PubMed2002

Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.

The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.

Amino Acid Sequence↗