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Genes Jan 2024Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing... (Review)
Review
Population-based biobanking is an essential element of medical research that has grown substantially over the last two decades, and many countries are currently pursuing large national biobanking initiatives. The rise of individual biobanks is paralleled by various networking activities in the field at both the national and international level, such as BBMRI-ERIC in the EU. A significant contribution to population-based biobanking comes from large cohort studies and national repositories, including the United Kingdom Biobank (UKBB), the CONSTANCES project in France, the German National Cohort (NAKO), LifeLines in the Netherlands, FinnGen in Finland, and the All of Us project in the U.S. At the same time, hospital-based biobanking has also gained importance in medical research. We describe some of the scientific questions that can be addressed particularly well by the use of population-based biobanks, including the discovery and calibration of biomarkers and the identification of molecular correlates of health parameters and disease states. Despite the tremendous progress made so far, some major challenges to population-based biobanking still remain, including the need to develop strategies for the long-term sustainability of biobanks, the handling of incidental findings, and the linkage of sample-related and sample-derived data to other relevant resources.
Topics: Humans; Biological Specimen Banks; Population Health; Biomedical Research; Calibration; Finland
PubMed: 38254956
DOI: 10.3390/genes15010066 -
RSC Chemical Biology Aug 2023This review summarizes the structures, biochemical properties, and mechanisms of two major biological sources of ethylene, the ethylene-forming enzyme (EFE) and... (Review)
Review
This review summarizes the structures, biochemical properties, and mechanisms of two major biological sources of ethylene, the ethylene-forming enzyme (EFE) and 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase (ACCO). EFE is found in selected bacteria and fungi where it catalyzes two reactions: (1) the oxygen-dependent conversion of 2-oxoglutarate (2OG) to ethylene plus three molecules of CO/bicarbonate and (2) the oxidative decarboxylation of 2OG while transforming l-arginine to guanidine and l-Δ-pyrroline-5-carboxylic acid. ACCO is present in plants where it makes the plant hormone by transforming ACC, O, and an external reductant to ethylene, HCN, CO, and water. Despite catalyzing distinct chemical reactions, EFE and ACCO are related in sequence and structure, and both enzymes require Fe(ii) for their activity. Advances in our understanding of EFE, derived from both experimental and computational approaches, have clarified how this enzyme catalyzes its dual reactions. Drawing on the published mechanistic studies of ACCO and noting the parallels between this enzyme and EFE, we propose a novel reaction mechanism for ACCO.
PubMed: 37654506
DOI: 10.1039/d3cb00066d -
Communications Biology Sep 2023Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on... (Review)
Review
Biofilms have conventionally been perceived as dense bacterial masses on surfaces, following the five-step model of development. Initial biofilm research focused on surface-attached formations, but detached aggregates have received increasing attention in the past decade due to their pivotal role in chronic infections. Understanding their nature sparked fervent discussions in biofilm conferences and scientific literature. This review consolidates current insights on non-attached aggregates, offering examples of their occurrence in nature and diseases. We discuss their formation and dispersion mechanisms, resilience to antibiotics and immune-responses, drawing parallels to surface-attached biofilms. Moreover, we outline available in vitro models for studying non-attached aggregates.
Topics: Anti-Bacterial Agents; Biofilms; Molecular Weight
PubMed: 37658117
DOI: 10.1038/s42003-023-05281-4 -
Trends in Neurosciences Oct 2023Postmitotic neurons require persistently active controls to maintain terminal differentiation. Unlike dividing cells, aberrant cell cycle activation in mature neurons... (Review)
Review
Postmitotic neurons require persistently active controls to maintain terminal differentiation. Unlike dividing cells, aberrant cell cycle activation in mature neurons causes apoptosis rather than transformation. In Alzheimer's disease (AD) and related tauopathies, evidence suggests that pathogenic forms of tau drive neurodegeneration via neuronal cell cycle re-entry. Multiple interconnected mechanisms linking tau to cell cycle activation have been identified, including, but not limited to, tau-induced overstabilization of the actin cytoskeleton, consequent changes to nuclear architecture, and disruption of heterochromatin-mediated gene silencing. Cancer- and development-associated pathways are upregulated in human and cellular models of tauopathy, and many tau-induced cellular phenotypes are also present in various cancers and progenitor/stem cells. In this review, I delve into mechanistic parallels between tauopathies, cancer, and development, and highlight the role of tau in cancer and in the developing brain. Based on these studies, I put forth a model by which pathogenic forms of tau disrupt the program that maintains terminal neuronal differentiation, driving cell cycle re-entry and consequent neuronal death. This framework presents tauopathies as conditions involving the profound toxic disruption of neuronal identity.
Topics: Humans; Alzheimer Disease; Tauopathies; Neurons; Brain; Stem Cells
PubMed: 37591720
DOI: 10.1016/j.tins.2023.07.006 -
Internal and Emergency Medicine Sep 2023Mounting experimental evidence from in vitro and in vivo animal studies points to an essential role of the CXCL8-CXCR1/2 axis in neutrophils in the pathophysiology of... (Review)
Review
Mounting experimental evidence from in vitro and in vivo animal studies points to an essential role of the CXCL8-CXCR1/2 axis in neutrophils in the pathophysiology of inflammatory and autoimmune diseases. In addition, the pathogenetic involvement of neutrophils and the CXCL8-CXCR1/2 axis in cancer progression and metastasis is increasingly recognized. Consequently, therapeutic targeting of CXCR1/2 or CXCL8 has been intensively investigated in recent years using a wide array of in vitro and animal disease models. While a significant benefit for patients with unwanted neutrophil-mediated inflammatory conditions may be expected from a potential clinical use of inhibitors, their use in severe infections or sepsis might be problematic and should be carefully and thoroughly evaluated in animal models and clinical trials. Translating the approaches using inhibitors of the CXCL8-CXCR1/2 axis to cancer therapy is definitively a new and promising research avenue, which parallels the ongoing efforts to clearly define the involvement of neutrophils and the CXCL8-CXCR1/2 axis in neoplastic diseases. Our narrative review summarizes the current literature on the activation and inhibition of these receptors in neutrophils, key inhibitor classes for CXCR2 and the therapeutic relevance of CXCR2 inhibition focusing here on gastrointestinal diseases.
Topics: Animals; Humans; Neoplasms; Neutrophils
PubMed: 37249756
DOI: 10.1007/s11739-023-03309-5 -
Molecular Diagnosis & Therapy Jan 2024The genetic background of inflammatory bowel disease, both Crohn's disease and ulcerative colitis, has been known for more than 2 decades. In the last 20 years,... (Review)
Review
The genetic background of inflammatory bowel disease, both Crohn's disease and ulcerative colitis, has been known for more than 2 decades. In the last 20 years, genome-wide association studies have dramatically increased our knowledge on the genetics of inflammatory bowel disease with more than 200 risk genes having been identified. Paralleling this increasing knowledge, the armamentarium of inflammatory bowel disease medications has been growing constantly. With more available therapeutic options, treatment decisions become more complex, with still many patients experiencing a debilitating disease course and a loss of response to treatment over time. With a better understanding of the disease, more effective personalized treatment strategies are looming on the horizon. Genotyping has long been considered a strategy for treatment decisions, such as the detection of thiopurine S-methyltransferase and nudix hydrolase 15 polymorphisms before the initiation of azathioprine. However, although many risk genes have been identified in inflammatory bowel disease, a substantial impact of genetic risk assessment on therapeutic strategies and disease outcome is still missing. In this review, we discuss the genetic background of inflammatory bowel disease, with a particular focus on the latest advances in the field and their potential impact on management decisions.
Topics: Humans; Genome-Wide Association Study; Inflammatory Bowel Diseases; Colitis, Ulcerative; Crohn Disease; Azathioprine
PubMed: 37847439
DOI: 10.1007/s40291-023-00678-7 -
Clinical and Experimental Emergency... Mar 2024The goal of a clinical study is to determine the factors associated with a disease and to assess the efficacy and safety of an investigational drug, procedure, or...
The goal of a clinical study is to determine the factors associated with a disease and to assess the efficacy and safety of an investigational drug, procedure, or device. Since clinical study designs vary due to unique requirements of individual studies, the aims of this report are to educate researchers on the different types of studies and to assist researchers in choosing the optimal study type to fulfill their individual requirements. Clinical studies are classified into the two main types, observational studies and clinical trials, depending on the presence or absence of an intervention. Observational studies include case-control studies, cohort studies, and cross-sectional studies. Case-control and cohort studies may be prospective or retrospective, and case-control studies may be nested or not. Clinical trials may be pragmatic and may be controlled or noncontrolled; randomized or nonrandomized; open label or blinded; and parallel, crossover, or factorial. These observational and clinical trial designs are reviewed. Each type of clinical study has advantages and disadvantages. Therefore, researchers must consider these in choosing the design best suited for achieving their study objectives.
PubMed: 37280050
DOI: 10.15441/ceem.23.036