Malaria screening: what is the contribution of molecular biology?

INTRODUCTION: According to the World Health Organization, Microscopy is the gold standard for diagnosing malaria. However, the performance of this examination depends on the experience of the microscopist and the level of parasitemia. Thus, molecular biology detection of malaria could be an alternative technique. AIM: evaluate the contribution of molecular biology in detecting imported malaria. METHODS: This was a descriptive, prospective study, including all students, from the Monastir region, and foreigners, from countries endemic to malaria. The study period was from September 2020 to April 2021. Each subject was screened for malaria by three methods: direct microscopic detection of Plasmodium, detection of plasmodial antigens, and detection of plasmodial DNA by nested PCR. RESULTS: Among the 127 subjects screened, only one had a positive microscopic examination for Plasmodium falciparum. Among the 126 subjects with a negative microscopic examination, twelve students had a positive nested PCR result, i.e. 9.5%. Molecular sequencing allowed the identification of ten isolates of Plasmodium falciparum, one Plasmodium malariae and one Plasmodium ovale. Our study showed that the results of nested PCR agreed with those of microscopy in 90.6% of cases. CONCLUSION: Nested PCR seems more sensitive for the detection of low parasitemias. Hence the importance of including molecular biology as a malaria screening tool to ensure better detection of imported cases.

Advancements in Structural Biology ­ How to See Molecules of Life? / Postepy biologii strukturalnej ­ jak zobaczyc czasteczki zycia?

Structural biology is focused on understanding the architecture of biomolecules, such as proteins and nucleic acids. Deciphering the structure helps to understand their function in the cell at a very precise ­ molecular level. This makes it possible to not only determine the basis of diseases but also to propose therapeutic strategies and tools. Such a strong motivation for the development of structural biology has led to the development of a number of methods, which enable determination of the structures of the molecules of life. The continuous progress has been enabled by the integration of biology, chemistry, physics, and computer science, making structural biology extremely interdisciplinary. In its 35-year history, the Institute of Bioorganic Chemistry of the Polish Academy of Sciences in Poznan has become one of the key Polish institutions conducting research in the field of structural biology. On one hand, the research has brought international recognition, and on the other hand, it has forced the implementation and development of cutting-edge methods. This review discusses the methods used in structural biology at the Institute.

Several supplementary concepts for applied category-theoretical states over an extended Petri net using an example relating to genetic coding: Toward an abstract algebraic formulation of molecular/genetic biology.

algebraic concepts such as category are considered cornerstones on which logical consistency relies in any sophisticated study of natural phenomena. However, to the best of our knowledge, in molecular/genetic biology, their application is still severely limited because they capture neither the dynamics nor provide a visual form. The Petri net (PN) has often been used to illustrate visually parallel, asynchronous dynamic events in small data systems. A prototypal hybrid model combining both category theory and extended PNs may instead be indispensable for that purpose. This hybrid model incorporates 1) token-like elements of a group, 2) object-like places of a category, 3) square poles (rather than pentagon poles) that enable unique identifications of single-strand DNA sequences from the shape of its polygonal line, 4) creation/annihilation morphisms that generate/erase tokens, 5) Cartesian products 'Z5×Z2ׅ' that enable conversions between DNA and RNA sequences, 6) somatic recombinations (VDJ recombinations) for antibodies displayed concretely in category-theoretic form, 7) 'identity protein Δ' translated from a triplet of identity bases 'EEE' as an advanced concept from our previous display of the canonical central dogma, 8) illustrations of an incidence-matrix-like matrix A that includes operators as coordinates, and 9) basic topics concerning the canonical central dogma being displayed concretely using concepts of conventional category theory such as 'adjoint', 'adjoint functor', 'natural transformation', 'Yoneda's lemma' and 'Kan extension'. These ideas provide more advanced tools that expand our previous model concerning nucleic-acid-base sequences. Despite the nascent nature of our methodology, our hybrid model has potential in a variety of applications, illustrated using molecular/genetic sequences, in particular providing a simple dynamic/visual representation. With further improvements, this approach may prove effective in reducing the need for large data-storing systems.

Advances in Molecular Plant Sciences.

In recent years, as biotechnological advancements have continued to unfold, our understanding of plant molecular biology has undergone a remarkable transformation [...].

Theory vs. experiment: The rise of the dynamic view of proteins.

Over the past century, the scientific conception of the protein has evolved significantly. This paper focuses on the most recent stage of this evolution, namely, the origin of the dynamic view of proteins and the challenge it posed to the static view of classical molecular biology. Philosophers and scientists have offered two hypotheses to explain the origin of the dynamic view and its slow reception by structural biologists. Some have argued that the shift from the static to the dynamic view was a Kuhnian revolution, driven by the accumulation of dynamic anomalies, while others have argued that the shift was caused by new empirical findings made possible by technological advances. I analyze this scientific episode and ultimately reject both of these empiricist accounts. I argue that focusing primarily on technological advances and empirical discoveries overlooks the important role of theory in driving this scientific change. I show how the application of general thermodynamic principles to proteins gave rise to the dynamic view, and a commitment to these principles then led early adopters to seek out the empirical examples of protein dynamics, which would eventually convince their peers. My analysis of this historical case shows that empiricist accounts of modern scientific progress-at least those that aim to explain developments in the molecular life sciences-need to be tempered in order to capture the interplay between theory and experiment.

Large language models reshaping molecular biology and drug development.

The utilization of large language models (LLMs) has become a significant advancement in the domains of medicine and clinical informatics, providing a revolutionary potential for scientific breakthroughs and customized therapies. LLM models are trained on large datasets and exhibit the capacity to comprehend and analyze intricate biological data, encompassing genomic sequences, protein structures, and clinical health records. With the utilization of their comprehension of the language of biology, they possess the ability to reveal concealed patterns and insights that may evade human researchers. LLMs have been shown to positively impact various aspects of molecular biology, including the following: genomic analysis, drug development, precision medicine, biomarker development, experimental design, collaborative research, and accessibility to specialized expertise. However, it is imperative to acknowledge and tackle the obstacles and ethical implications involved. The careful consideration of data bias and generalization, data privacy and security, explainability and interpretability, and ethical concerns around responsible application is vital. The successful resolution of these obstacles will enable us to fully utilize the capabilities of LLMs, leading to substantial progress in the fields of molecular biology and pharmaceutical research. This progression also has the ability to bolster influential impacts for both the individual and the broader community.

[Contributions of molecular biology to the management of colorectal cancer]. / Apports de la biologie moléculaire dans la prise en charge du cancer colorectal.

CONTRIBUTIONS OF MOLECULAR BIOLOGY TO THE MANAGEMENT OF COLORECTAL CANCER. Colorectal cancer (CRC) is a major public health problem affecting almost 43.000 people a year and causing 17.000 deaths. Advances in molecular biology have made it possible to identify some of the mechanisms involved in colorectal carcinogenesis and tumor proliferation. Some molecular alterations are now routinely investigated to adapt follow-up and therapeutic decisions in both localized and metastatic CRC.

BIOLOGIE MOLÉCULAIRE ET PRISE EN CHARGE DU CANCER COLORECTAL. Le cancer colorectal (CCR) est un problème de santé publique majeur qui touche près de 43 000 personnes par an et cause 17 000 décès. Les progrès de la biologie moléculaire ont permis d'identifier certains des mécanismes impliqués dans la carcinogenèse colorectale et la prolifération tumorale. Certaines altérations moléculaires sont désormais recherchées en pratique courante pour adapter le suivi et la décision thérapeutique dans les CCR localisés et métastatiques.

Report on the 2nd international molecular biosciences PhD and postdoc conference 2023: The emerging challenge - environmental impacts on human health.

The 2nd International FEBS-IUBMB-ENABLE Molecular Biosciences PhD and Postdoc Conference was held from 23rd to 25th November 2023 in Cologne, Germany. Over 240 participants from 31 different countries came together at the University of Cologne to follow the two-day scientific symposium and the career day. This year's topic was "The emerging challenge - environmental impacts on human health". In four different sessions, eight renowned keynote speakers presented their current research. By offering flash and short talks, 39 participants were able to present their work in front of a big audience. Scientific exchange and networking were encouraged during the two poster sessions, during breaks, and the conference dinner. On the Career Day, a career fair was held and participants could attend workshops as well as career chats to improve their job prospects. The success of the series will be continued during the next conference edition: "Artificial Intelligence - Reshaping biomedical and healthcare research", which will take place 4th to 6th December 2024 in Singapore.

Highlights from the 2023 International Meeting on the Molecular Biology of Hepatitis B virus.

Since its discovery in 1965, our understanding of the hepatitis B virus (HBV) replication cycle and host immune responses has increased markedly. In contrast, our knowledge of the molecular biology of hepatitis delta virus (HDV), which is associated with more severe liver disease, is less well understood. Despite the progress made, critical gaps remain in our knowledge of HBV and HDV replication and the mechanisms underlying viral persistence and evasion of host immunity. The International HBV Meeting is the leading annual scientific meeting for presenting the latest advances in HBV and HDV molecular virology, immunology, and epidemiology. In 2023, the annual scientific meeting was held in Kobe, Japan and this review summarises some of the advances presented at the Meeting and lists gaps in our knowledge that may facilitate the development of new therapies.

The Molecular Genetics and Genomics of Plant-Pathogen Interactions.

Plants have evolved an intricate immune system to protect themselves from potential pathogens [...].

Deciphering the molecular biology of inflammatory breast cancer through molecular characterization of patient samples and preclinical models.

Inflammatory breast cancer is an aggressive subtype of breast cancer with dismal patient prognosis and a unique clinical presentation. In the past two decades, molecular profiling technologies have been used in order to gain insight into the molecular biology of IBC and to search for possible targets for treatment. Although a gene signature that accurately discriminates between IBC and nIBC patient samples and preclinical models was identified, the overall genomic and transcriptomic differences are small and ambiguous, mainly due to the limited sample sizes of the evaluated patient series and the failure to correct for confounding effects of the molecular subtypes. Nevertheless, data collected over the past 20 years by independent research groups increasingly support the existence of several IBC-specific biological characteristics. In this review, these features are classified as established, emerging and conceptual hallmarks based on the level of evidence reported in the literature. In addition, a synoptic model is proposed that integrates all hallmarks and that can explain how cancer cell intrinsic mechanisms (i.e. NF-κB activation, genomic instability, MYC-addiction, TGF-ß resistance, adaptive stress response, chromatin remodeling, epithelial-to-mesenchymal transition) can contribute to the establishment of the dynamic immune microenvironment associated with IBC. It stands to reason that future research projects are needed to further refine (parts of) this model and to investigate its clinical translatability.

[Molecular biology analysis of 2 rare RhD variant individuals with RHD*DEL37].

The Rh blood grouping system is a critical standardized test in transfusion medicine, especially for the cases related to haemolytic transfusion reactions and neonatal haemolytic disease caused by clinical RhD blood group incompatibility. In the present case report, we presented two cases with the uncommon RHD gene variation RHD*DEL37. The blood samples of the two subjects were mistakenly identified as RhD-negative through conventional serological testing. Firstly, both blood samples were tested negative for the RhD antigen using traditional tube test and gel microcolumn methods. The phenotyping of RhCE were identified as ccEe and ccee for each sample, respectively. Secondly, genetic analysis was performed using polymerase chain reaction-sequence specific prime (PCR-SSP) which revealed that neither sample belonging to the several common RHD gene variants which was found in Asia. Moreover, they turned out to be positive for the RHD haplotype, which indicated that exons 1-10 on one of the RHD alleles were entirely absent. In addition, a T>C mutation was observed at bases 1154-31 in intron 8 of the other allele, which was located at the intron 8 breakpoint. This result was obtained after further Sanger sequencing of exons 1-10 of the RHD gene. The mutant allele was designated as RHD*DEL37 by the International Society of Blood Transfusion (ISBT) and was identified as D-elute(Del) by phenotype ana-lysis. Both samples were genotyped as RHD*DEL37 and showed positive results. In summary, the true genotype of the two blood samples, of which the screening results only using serological testing method was negative, were RHD*DEL37 /RHD-(RHD*01N.01). Notably, this kind of genotype was reported for the first time in Chinese population. Moreover, the two individuals did not have ties of consanguinity, indicating that some of the Chinese individuals could be carriers of the genetic mutation. Therefore, it might be necessary to further confirm the frequency of this mutation in the Chinese population and the possibility of homozygosity for this mutation. This report identifies infrequent RHD gene mutation samples by coupling molecular biology and serological methods to prevent misclassification of blood groups. Combining serological and molecular biology test results to determine blood group is critical in protecting patients during clinical transfusion procedures.

Adopting Mechanistic Molecular Biology Approaches in Exposome Research for Causal Understanding.

Through investigating the combined impact of the environmental exposures experienced by an individual throughout their lifetime, exposome research provides opportunities to understand and mitigate negative health outcomes. While current exposome research is driven by epidemiological studies that identify associations between exposures and effects, new frameworks integrating more substantial population-level metadata, including electronic health and administrative records, will shed further light on characterizing environmental exposure risks. Molecular biology offers methods and concepts to study the biological and health impacts of exposomes in experimental and computational systems. Of particular importance is the growing use of omics readouts in epidemiological and clinical studies. This paper calls for the adoption of mechanistic molecular biology approaches in exposome research as an essential step in understanding the genotype and exposure interactions underlying human phenotypes. A series of recommendations are presented to make the necessary and appropriate steps to move from exposure association to causation, with a huge potential to inform precision medicine and population health. This includes establishing hypothesis-driven laboratory testing within the exposome field, supported by appropriate methods to read across from model systems research to human.

The journey from bench to bedside-it takes a science village.

I was fortunate enough to start my career at what was the dawn of modern-day molecular biology and to apply it to an important health problem. While my early work focused on fundamental science, the desire to understand human disease better and to find practical applications for research discoveries resulted, over the following decades, in creating a stream of translational research directed specifically toward epithelial cancers. This could only have been possible through multiple collaborations. This type of team science would eventually become a hallmark of my career. With the development of higher throughput molecular techniques, the pace of research and discovery has quickened, and the concept of personalized medicine based on genomics is now coming to fruition. I hope my legacy will not just reflect my published works, but will also include the impact I have had on the development of the next generation of scientists and clinician scientists who inspired me with their dedication, knowledge, and enthusiasm.

[Clinicopathological and molecular genetic features of Crohn's disease].

Objective: To investigate the clinicopathological and molecular genetic characteristics of Crohn's disease (CD). Methods: A retrospective analysis was conducted on 52 CD patients who underwent surgical resection at the First Affiliated Hospital of Nanjing Medical University between January 2014 and June 2023. Clinical presentations and histopathological features were assessed. Whole-genome sequencing was performed on 17 of the samples, followed by sequencing and pathway enrichment analyses. Immunohistochemistry was used to assess the expression of frequently mutated genes. Results: Among the 52 patients, 34 were males and 18 were females, male-to-female ratio was 1.9∶1.0, with a median age of 45 years at surgery and 35 years at diagnosis. According to the Montreal classification, A3 (51.9%,27/52), B2 (61.5%, 32/52), and L3 (50.0%,26/52) subtypes were the most predominant. Abdominal pain and diarrhea were the common symptoms. Histopathological features seen in all 52 patients included transmural inflammation, disruption of cryptal architecture, lymphoplasmacytic infiltration, varying degrees of submucosal fibrosis and thickening, increased enteric nerve fibers and neuronal proliferation. Mucosal defects, fissure ulcers, abscesses, pseudopolyps, and adenomatous proliferation were also observed in 51 (98.1%), 38 (73.1%), 28 (53.8%), 45 (86.5%), and 28 (53.8%) cases, respectively. Thirty-one (59.6%) cases had non-caseating granulomas, and 3 (5.8%) cases had intestinal mucosal glandular epithelial dysplasia. Molecular analysis showed that 12/17 CD patients exhibited mutations in at least one mucin family gene (MUC2, MUC3A, MUC4, MUC6, MUC12, MUC17), and MUC4 was the most frequently mutated in 7/17 of cases. Immunohistochemical stains showed reduced MUC4 expression in epithelial cells, with increased MUC4 expression in the epithelial surface, particularly around areas of inflammatory cell aggregation; and minimal expression in the lower half of the epithelium. Conclusions: CD exhibits diverse clinical and pathological features, necessitating a comprehensive multidimensional analysis for diagnosis. Mutations and expression alterations in mucin family genes, particularly MUC4, may play crucial roles in the pathogenesis of CD.