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PubMed1977

A view of the background of Freudian theory.

A major concern of nineteenth century scientists was to delineate the objective units or entities with which science deals. While some philosophers of science abandoned the search as futile and tried to redefine science, investigators in the biological sciences and the sciences of man attempted to discover new entities upon which to base their disciplines. A new understanding of hypnotism gave Freud the opportunity to isolate objective entities within the mind and to found a psychology on that basis.

Animals↗
PubMed2022

Direct capture and sequencing reveal ultra-short single-stranded DNA in biofluids.

Cell-free DNA (cfDNA) has become the predominant analyte of liquid biopsy; however, recent studies suggest the presence of subnucleosomal-sized DNA fragments in circulation that are likely single-stranded. Here, we report a method called direct capture and sequencing (DCS) tailored to recover such fragments from biofluids by directly capturing them using short degenerate probes followed by single strand-based library preparation and next-generation sequencing. DCS revealed a new DNA population in biofluids, named ultrashort single-stranded DNA (ussDNA). Evaluation of the size distribution and abundance of ussDNA manifested generality of its presence in humans, animal species, and plants. In humans, red blood cells were found to contain abundant ussDNA; plasma-derived ussDNA exhibited modal size at 50 nt. This work reports the presence of an understudied DNA population in circulation, and yet more work is awaiting to study its generation mechanism, tissue of origin, disease implications, etc.

Biological sciences↗
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↗
PubMed1977

New vistas for the study of structural and functional dynamics of the heart, lungs, and circulation by noninvasive numerical tomographic vivisection.

Major segments of the biologic sciences and the practice of medicine are based on study and knowledge of the relationships of anatomic structure to biologic function. Traditionally, this knowledge has been gained by indirect means, inference, or by direct surgical vivisection or postmortem examination. The revolutionary capability of nondestructive, operator interactive, mathematical vivisection provided by synchronous cylindrical scanning tomography to obtain similar information non-invasively and painlessly will provide these data to the internist for individual patients. Furthermore, this information will be in a computerized format which can be subjected to myriad types of objective measurements and display. These developments promise beneficial effects of clinical diagnosis and health care which may approach those associated with the discoveries of the biomedical investigative and clinical diagnostic value of X-rays and cardiac catheterization.

Angiography↗
PubMed1977

Models of membranes of cerebral cells as substrates for information storage.

The past decade has seen a growing understanding of functional capacities and structural organization of cell membranes. Studies in immunology, endocrinology and neurobiology have led to some unifying concepts about processes of transduction at the membrane surface, and the coupling of surface events to the interior of the cell. My interest in these problems has been directed in no small measure by interactions with Lars Onsager. His kindly tutelage and rigorous criticism have been a source of endless encouragement to those who sought the full measure of his wisdom in the difficult area of the energetics of membrane excitation. Onsager's unflagging interest in mechanisms of ion transportation led him to earnest consideration of a variety of non-classical models of conduction in proteins, always tempered by his deep insight essential aspects of physical chemistry. My discussions with him at the MIT Neuroscience Research Program were a regular stimulus to the experiments which our groups have undertaken in search of answers to questions raised by the models presented here. Above all, Lars Onsager was a kindly, gentle man. In this personal example, he will be as sadly missed as for his broad and imaginative approach to critical questions in the physical and biological sciences.

Animals↗
PubMed1976

Clinical science.

The most obvious achievements of clinical science have been in the elucidation of symptoms and signs and the patterns of disordered function due to failure of the organs or to nutritional disturbances. The benefits of clinical research are both direct--through improved practice--and indirect--through improved teaching and contributions to biological science. It is suggested that the clinical scientist, experienced in both clinical and research work, has a potential not to be expected from collaboration between non-scientific clinicians and non-clinical scientists. Problems which particularly affect clinical research include: ethics; difficulty in being experimentally rigorous; the need to be opportunistic; dependence on transient workers; excessive conern with the end stages of irreversible disease; triviality; uncritical and premature imitation of research in practice. Clinical science is always threatened by a tendency for its problems to be regarded simply as applied problems of basic science. The roles of the clinical scientist should include: elucidating clinical phenomena, about most of which we remain very ignorant; collaboration with basic scientists on the one hand and with community scientists on the other; and clarifying the description and analysis of illnesses.

Disease↗
PubMedDate not supplied

Radiopharmacology. (The state of the art).

The past, present and future development of radiopharmacology as a new branch of science is being presented. Radiopharmacological techniques have been applied by many scientists in the past, not knowing that they were developing a new scientific field. With the advancement of these techniques, the creation of a specialized teaching program and the organization of the first international symposium on radiopharmacology, the first specialized meeting in this area, radiopharmacology became a discipline standing on its own feet. The main purpose of radiopharmacology is to study the chemical properties of radiotracers, and their interactions with living organisms. In order to promote and further expand this field, an international association of radiopharmacology was created. The main purpose of the association is to congregate all those interested in the uses of radiotracers in biological sciences, including medicine, by the organization of national and international meetings.

Biological Availability↗
PubMed1979

Biologic correlates of psychoanalytic concepts.

In deference to Freud's ingenious predictions of the future potential of the biological sciences concerning psychoanalytic tenets and clinical disorders, an attempt is made to bring the concepts of the Three Polarities, life and death instincts, the Unconscious, and repression into association with relevant anatomical, neurophysiological, and neurochemical data. Implications for diagnosis and therapy were considered in the light of recent and anticipated neurobiological advances. Building bridges between biologic and physiologic processes is exceedingly complicated by the enormous complexities of both fields. There is good reason to hope that the speculative nature which at this time pervades our bridging efforts will eventually be substituted by unequivocal facts and deductions.

Aggression↗
PubMed2025

How Have Massively Parallel Sequencing Technologies Furthered Our Understanding of Oncogenesis and Cancer Progression?

Massively parallel sequencing technologies have been a boon to many fields of biological science, including oncology. Cancer is an umbrella term for many diseases featuring abnormal cellular growth due to genetic and epigenetic aberrations. Advances in sequencing technology allow for interrogation of the DNA and RNA of cancer cells and other cells in the tumor microenvironment down to a single-base resolution. However, these strides come after a rich history of ground-breaking biological assays, like the discovery of the Philadelphia chromosome in the context of leukemia. Many specific genetic and epigenetic modifications have been implicated in oncogenesis, cancer progression, and response to treatment. Sequencing technologies have also helped to associate populations of bacteria in the microbiome to cancer development and prognosis. However, all this new information, especially when procured via high-throughput methods, comes at the cost of being more computationally and staff-resource intensive. There is also more risk to the privacy of the individuals with sequenced genomes. Notwithstanding, the overall benefit of sequencing technologies can greatly outweigh the risks with careful advancements and continued focus on the goal: helping those affected by cancer via precision medicine. Cancer biology has been and will continue to be elucidated by sequencing innovations in ways unimaginable without it.

Humans↗
PubMed1977

[Planned control of reproduction processes in industrialized pig production].

A planned process of concentration and specialisation in pig production has been introduced in the USSR, GDR, and other socialist countries in recent years and is likely to open up wider opportunities for the use of up-to-date technologies and latest findings of the biological sciences. Large-scale use of bio-engineering and methods of reproduction control is quite logical, in this context. This will provide a real chance for cyclogram control of all events important to management, planning, and follow-up of reproduction processes and for a planful implementation of industrialised production methods. Processes of cycle control are being increasingly applied to industrialised sow breeding units against the background of artificial insemination of pigs which is gaining widespread popularity after its emphasised introduction in the USSR. Research and field results regarding biological engineering in sow of oestrus, ovulation, pregnancy, and birth are reported in this paper and will, hopefully, help in determining mating and farrowing deadlines for breeding on the basis of artificial insemination and, consequently, contribute to widest possible programming of life cycles for the breeding animals concerned.

Animals↗
PubMed1975

[Veterinary genetics].

At the age of scientific and technical progress and of industrialization of animal husbandry neither theoretical nor applied science can dispense with the data of the veterinary genetics. Unfortunately this branch of science does not receive the attention it deserves. The following three problems have to be solved by the veterinary genetics: (1) the investigation of the relationship between the heredity and the pathology of animals; the examination of the mechanism of pathology at the molecular and organism genetic levels; (2) the elaboration of the methods of genetic diagnostics; (3) the search for scientifically-substantiated directions in breeding of animal breeds highly resistant to diseases. The main attention will be paid to the investigation of the mechanisms ensuring the natural resistance of animals to certain definite diseases. The establishment and development of veterinary genetics will exert a favourable influence on the progress of biological sciences. Its data will be indispensable both for the theory and the practice of agriculture.

Animal Diseases↗
PubMed1976

[The concept of health and disease].

1. The author reviews some current concepts concerning the definitions and uses of the concepts of health and illness. Starting from the definitions in Psychiatry, "normality" is considered from the statistic, the normative and the clinical standpoints, and as a part of a continuum stretching from health to illness. Several approaches are analyzed, among which Wittaker's, who sets forth the following indicators of normality: a) self-knowledge; b) self-esteem; c) self-security; d) capacity for giving and receiving affection; e) satisfaction of corporal needs; f) productivity and capacity for happiness; g) lack of tensions and of hipersensitivity. 2. The concept of illness as an operative concept is also analyzed, leading to the following statements: a) it is inexistent in non-biological sciences; b) it appears in social sciences only through extrapolation; c) in medicine it means the breacking of homeosthasis; d) in psychology and dynamic psychiatry it means the abnormal stressing of normal mechanisms, common to all persons. 3. The concept of health as equilibrium is also analyzed, with the following precisions: a) equilibrium is defined within a system as affecting the whole of it, and implying transformation and self-regulation; b) homeosthasis is a case of equilibrium for steady complex systems; c) adaptation is the maintenance of equilibrium when there are exchanges with the evironment. 4. Finally, those concepts are applied to mental illness and its limits, and the following criteria are set forth: a) amount of anguish; b) depression related to its motives, intensity, persistence and frequency; c) regression to previous development stages; d) use of defense mechanisms in an inadequate or stereotyped way.

Adaptation, Biological↗
PubMed2026

CAKR: commutative algebra k-mer representations for genomics.

Despite the availability of various sequence analysis models, comparative genomic analysis remains a challenge in genomics, genetics, and phylogenetics. Commutative algebra, a fundamental tool in algebraic geometry and number theory, has rarely been used in data and biological sciences. In this study, we introduce commutative algebra k-mer representations as a nonlinear algebraic framework for analyzing genomic sequences. This representation bridges commutative algebra, algebraic topology, combinatorics, and machine learning to establish a mathematical framework for comparative genomic analysis. We evaluate its effectiveness on three tasks including genetic variant classification, phylogenetic tree reconstruction, and viral classification, typically requiring alignment-based, alignment-free, and machine-learning approaches, respectively. In this work, we show that commutative algebra k-mer representations outperform five state-of-the-art sequence analysis methods across twelve primary datasets, with two additional supplementary fragment-placement benchmarks, especially in viral classification, and maintain relatively stable predictive accuracy as dataset size increases, underscoring scalability and robustness.

Genomics↗
PubMed1975

Scientific methodology applied.

The subject of this symposium is naproxen, a new drug that resulted from an investigation to find a superior anti-inflammatory agent. It was synthesized by Harrison et al. in 1970 at the Syntex Institute of Organic Chemistry and Biological Sciences. How can we chart the evolution of this or any other drug? Three steps are necessary: first, chemical studies (synthesis, analysis); second, animal pharmacology; third, human pharmacology. The last step can additionally be divided into four phases: metabolism and toxicology of the drug in normal volunteers; dose titration and initial clinical trials with sick subjects (pharmacometry); confirmatory clinical trials when the drug is accepted on the market and revaluation (familiarization trials). To discover the truth about naproxen, we must all participate actively with a critical mind, following the principles of scientific methodology. We shall find that the papers to be presented today all deal with the third step in the evaluation process--clinical pharmacology. It is quite evident that the final and most decisive test must be aimed at the most valuable target: the human being. The end product of this day's work for each of us should be the formation of an opinion based on solid scientific proofs. And let us hope that we will all enjoy fulfilling the symposium in its entire etymological meaning this evening. In vino veritas.

Animals↗
PubMed1975

The uses and limitations of radioisotopes in the investigation of gastrointestinal diseases.

Advances in the physical and biological sciences have in recent years led to a rapidly increasing use of radioactive agents in clinical medicine. The distinctive properties of these agents have made them invaluable for a large variety of unique in vivo and in vitro diagnostic tests. In order to help the clinician employ such tests productively and realistically, we have attempted to review the present status of radiosotopes with regard to gastrointestinal diseases. Emphasis has been placed not only on their value but also on their limitations; the degree of safety for in vivo application has also been briefly considered.

Adult↗
PubMed1979

Ethics of psychopharmacological research.

1. Psychiatry is in dire need of research in all areas--from psychopharmacology to psychotherapy. 2. It is unethical not to undertake research as long as hundreds of thousands of patients suffer from incapacitating mental disorders. 3. It is unethical not to apply proper research principles to obtain maximal information from the observations of patients treated by different drugs or techniques. 4. The Tokyo (Helsinki II) declaration takes cognizance of the special problems in psychiatric (and certain other areas of) research, and should help to heighten the standard of all clinical research. 5. Psychopharmacology is based on the principles of the biological sciences. In the behavioral aspects of clinical psychopharmacological research non-objective observations cannot solely be based on these principles, but we should always be able to aim at: a. Description of spontaneous history. b. Description of diagnostic and therapeutic techniques and processes. c. Description of goals. d. Description of results (with as detailed information on treatment failures as on treatment successes). e. Prospective studies instead of retrospective ones. 6. Psychopharmacology is probably the area within psychiatry where the ethical issues have been most protected against the uncritical introduction of unproven therapeutic principles.

Ethics, Medical↗
PubMed2025

Global diversity and evolution of Salmonella enterica serovar Panama: a genomic epidemiology study.

BACKGROUND: Non-typhoidal Salmonella is a globally important bacterial pathogen, typically associated with foodborne gastrointestinal infection. Some non-typhoidal Salmonella serovars can also colonise typically sterile sites in people to cause invasive non-typhoidal Salmonella disease. Salmonella enterica serovar Panama is responsible for a substantial number of cases of human bloodstream infection, but despite its global dissemination, numerous outbreaks, and a reported association with invasive non-typhoidal Salmonella disease, S enterica serovar Panama (S Panama) is understudied. We aimed to describe the genomic epidemiology and evolutionary history of S Panama to provide a vital baseline of understanding for this globally important serovar. METHODS: In this genomic epidemiology study, we analysed S Panama genomes derived from historical collections, national surveillance datasets, and publicly available epidemiological and whole-genome sequencing data which span the years 1931-2019. Maximum likelihood and Bayesian phylodynamic approaches were used to investigate population structure and evolutionary history and to infer geotemporal dissemination. A combination of different bioinformatic approaches with short-read and long-read data were used to characterise geographical and clade-specific trends in antimicrobial resistance (AMR) and genetic markers for invasiveness. FINDINGS: We analysed 836 S Panama genomes, of which 559 (67%) were sequenced as part of this study. The collection represents all inhabited continents and includes isolates collected between 1931 and 2019. We identified the presence of four geographically linked S Panama clades (C1 [ie, the Latin America and the Caribbean clade; n=338], C2 [ie, the European clade; n=124], C3 [ie, the Martinique clade; n=131], and C4 [ie, the Asia and Oceania clade; n=104]) and regional trends in AMR profiles. Most isolates (715 [86%] of 836) were pan-susceptible to antibiotics and belonged to clades circulating in Latin America and the Caribbean (64%, n=458). Most antibiotic-resistant isolates in our collection (113 [93%] of 121) fell within clades C4 (ie, the Asia and Oceania clade) and C2 (ie, the European clade), the latter of which had the highest invasiveness index values based on the conservation of 196 extraintestinal predictor genes. INTERPRETATION: This first large-scale phylogenetic analysis of S Panama has revealed important information about the population structure, AMR, global ecology, and genetic markers of invasiveness of the identified genomic subtypes. Our findings provide an important baseline for understanding S Panama infection. The presence of multidrug-resistant clades with elevated invasiveness index values should be monitored through ongoing surveillance, as such clades could pose an increased public health risk. FUNDING: UK Research and Innovation Global Challenges Research Fund and Biotechnology and Biological Sciences Research Council, UK Medical Research Council, Wellcome Trust, John Lennon Memorial Scholarship, Institut Pasteur, Santé publique France, Fondation Le Roch-Les Mousquetaires, Investissement d'Avenir Programme, and Australian National Health and Medical Research Council.

Humans↗