-
NAR Genomics and Bioinformatics Jun 2024In eukaryotes, translation initiation is a highly regulated process, which combines regulatory sequences located on the messenger RNA along with acting factors like...
In eukaryotes, translation initiation is a highly regulated process, which combines regulatory sequences located on the messenger RNA along with acting factors like eukaryotic initiation factors (eIF). One critical step of translation initiation is the start codon recognition by the scanning 43S particle, which leads to ribosome assembly and protein synthesis. In this study, we investigated the involvement of secondary structures downstream the initiation codon in the so-called START (STructure-Assisted RNA translation) mechanism on AUG and non-AUG translation initiation. The results demonstrate that downstream secondary structures can efficiently promote non-AUG translation initiation if they are sufficiently stable to stall a scanning 43S particle and if they are located at an optimal distance from non-AUG codons to stabilize the codon-anticodon base pairing in the P site. The required stability of the downstream structure for efficient translation initiation varies in distinct cell types. We extended this study to genome-wide analysis of functionally characterized alternative translation initiation sites in . This analysis revealed that about 25% of these sites have an optimally located downstream secondary structure of adequate stability which could elicit START, regardless of the start codon. We validated the impact of these structures on translation initiation for several selected uORFs.
PubMed: 38863530
DOI: 10.1093/nargab/lqae065 -
Journal of Magnetic Resonance Imaging :... Jun 2024Whether fetal cardiothoracic ratio (CTR) is constant or increasing with gestational age (GA) is controversial. The majority of the fetal CTR data has been obtained...
BACKGROUND
Whether fetal cardiothoracic ratio (CTR) is constant or increasing with gestational age (GA) is controversial. The majority of the fetal CTR data has been obtained through ultrasound.
PURPOSE
To retrospectively analyze CTR of diameter, area, and circumference on prenatal MR images in a low-risk population of singleton pregnancies, and to clarify its diagnostic value.
STUDY TYPE
Retrospective.
SUBJECTS
1024 low-risk singleton pregnancies undergoing MRI.
FIELD STRENGTH
Balanced steady state free precession sequence and single shot-fast spin echo sequence at 1.5 Tesla.
ASSESSMENT
Pregnancy clinical data were recorded and diameter, area, and circumference of the fetal heart and thorax were measured by two researchers with 6 and 7 years of radiology experience, respectively, and their variation with GA was investigated. The relationship between CTRs with GA was also investigated. Finally, the value of CTR in the diagnosis of fetuses with abnormal development was explored by using receiver operating characteristic (ROC) curves.
STATISTICAL TESTS
Linear regression and ROC curves. A P value <0.05 was considered significant.
RESULTS
There were significant positive linear correlations (R > 0.7, P < 0.0001) between the diameter, area, and circumference of the heart and thorax with GA. The CTRs remain constant values and do not change with GA. The 5th, 50th, and 95th percentiles of the CTR in 21-38 weeks GA were 0.32, 0.39, and 0.48 respectively. The corresponding percentiles for the area ratio were 0.15, 0.21 and 0.27, respectively, and for the circumference ratio were 0.40, 0.46, and 0.52, respectively. Based on ROC curves of CTR with three methods, the area under curves (AUCs) were up to 0.95, the sensitivity and the specificity were more than 88%.
DATA CONCLUSION
Reference ranges of fetal CTR were established using MRI, which remain constant. These may be helpful in making a definitive diagnosis in fetuses with abnormal development.
TECHNICAL EFFICACY
Stage 2.
PubMed: 38847618
DOI: 10.1002/jmri.29482 -
World Journal of Surgical Oncology May 2024In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence...
BACKGROUND
In clinical practice, genetic testing has become standard for many cancerous diseases. While a diagnosis of a single hereditary syndrome is not uncommon, the coexistence of two genetic diseases, even with partially common symptoms, remains unusual. Therefore, targeted next-generation sequencing (NGS), along with genetic consultation and imaging studies, is essential for every patient with confirmed paraganglioma. In this report, we present two sisters diagnosed with multiple endocrine neoplasia type 2 (MEN2A) and familial paraganglioma syndrome type 1 (FPGL1).
CASE PRESENTATION
After presenting to the clinic with neck tumors persisting for several months, both patients underwent tumor removal procedures following imaging and laboratory studies. Pathological reports confirmed the diagnosis of paragangliomas. Subsequently, genetic testing, including NGS, revealed a mutation in the rearranged during transfection (RET) gene: the heterozygous change (c.2410G > A), (p.Val804Met), and a variant of the succinate dehydrogenase complex subunit D (SDHD) gene: (c.64 C > T), (p.Arg22Ter). Subsequently, thyroidectomy procedures were scheduled in both cases.
CONCLUSION
To the best of our knowledge, this is the first report presenting these two mutations in two related patients, resulting in distinctive genetic syndromes with similar manifestations. This underscores that although infrequent, multiple hereditary disorders may co-occur in the same individual.
Topics: Humans; Female; Multiple Endocrine Neoplasia Type 2a; Siblings; Succinate Dehydrogenase; Adult; Proto-Oncogene Proteins c-ret; Prognosis; Thyroidectomy; Mutation; Genetic Testing; Pedigree; Paraganglioma; High-Throughput Nucleotide Sequencing
PubMed: 38802890
DOI: 10.1186/s12957-024-03418-1 -
Journal of Clinical Medicine Research Apr 2024A 67-year-old woman was admitted to the Hematology Department in 2014 with complaints of weakness and a low-grade fever. After conducting various tests, it was confirmed...
A 67-year-old woman was admitted to the Hematology Department in 2014 with complaints of weakness and a low-grade fever. After conducting various tests, it was confirmed that she had Waldenstrom macroglobulinemia. She underwent several rounds of chemotherapy and maintenance therapy with rituximab, which resulted in a good clinical response. However, in 2019, an abnormal growth in the soft tissues of patient's frontal region was discovered, which was diagnosed as lymphoplasmacytic lymphoma. This later progressed to an intracranial lesion. The patient underwent radiation therapy for both the extramedullary and intracranial growths, which had a positive effect. A year later, she developed a lesion in her lymph nodes and soft tissues of her right leg, which was confirmed to be a recurrence of Waldenstrom disease. She underwent further treatment and is currently in complete remission. This case highlights the rare occurrence of relapse in Waldenstrom disease and the challenges in diagnosing extramedullary lesions. It also demonstrates the success of modern treatment approaches using a combination of therapies.
PubMed: 38715560
DOI: 10.14740/jocmr5115 -
Biomedicine & Pharmacotherapy =... Jun 2024Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the... (Review)
Review
Relationships between protective enzymatic and non-enzymatic pro-antioxidant mechanisms and addictive substances use disorders (SUDs) are analyzed here, based on the results of previous research, as well as on the basis of our current own studies. This review introduces new aspects of comparative analysis of associations of pro-antixidant and neurobiological effects in patients taking psychoactive substances and complements very limited knowledge about relationships with SUDs from different regions, mainly Europe. In view of the few studies on relations between antioxidants and neurobiological processes acting in patients taking psychoactive substances, this review is important from the point of view of showing the state of knowledge, directions of diagnosis and treatment, and further research needed explanation. We found significant correlations between chemical elements, pro-antioxidative mechanisms, and lipoperoxidation in the development of disorders associated with use of addictive substances, therefore elements that show most relations (Pr, Na, Mn, Y, Sc, La, Cr, Al, Ca, Sb, Cd, Pb, As, Hg, Ni) may be significant factors shaping SUDs. The action of pro-antioxidant defense and lipid peroxidation depends on the pro-antioxidative activity of ions. We explain the strongest correlations between Mg and Sb, and lipoperoxidation in addicts, which proves their stimulating effect on lipoperoxidation and on the induction of oxidative stress. We discussed which mechanisms and neurobiological processes change susceptibility to SUDs. The innovation of this review is to show that addicted people have lower activity of dismutases and peroxidases than healthy ones, which indicates disorders of antioxidant system and depletion of enzymes after long-term tolerance of stressors. We explain higher level of catalases, reductases, ceruloplasmin, bilirubin, retinol, α-tocopherol and uric acid of addicts. In view of poorly understood factors affecting addiction, analysis of interactions allows for more effective understanding of pathogenetic mechanisms leading to formation of addiction and development the initiation of directed, more effective treatment (pharmacological, hormonal) and may be helpful in the diagnosis of psychoactive changes.
Topics: Humans; Antioxidants; Substance-Related Disorders; Oxidative Stress; Lipid Peroxidation; Animals; Neurobiology
PubMed: 38692055
DOI: 10.1016/j.biopha.2024.116604 -
Radiology Apr 2024See also the article by Lenkinski and Rofsky in this issue. See also the article by McKee et al in this issue.
See also the article by Lenkinski and Rofsky in this issue. See also the article by McKee et al in this issue.
Topics: Humans; Magnetic Resonance Imaging; Greenhouse Gases
PubMed: 38652029
DOI: 10.1148/radiol.240588 -
Chembiochem : a European Journal of... Apr 2024Understanding the mechanisms of drug action in malarial parasites is crucial for the development of new drugs to combat infection and to counteract drug resistance....
Understanding the mechanisms of drug action in malarial parasites is crucial for the development of new drugs to combat infection and to counteract drug resistance. Proteomics is a widely used approach to study host-pathogen systems and to identify drug protein targets. Plasmodione is an antiplasmodial early-lead drug exerting potent activities against young asexual and sexual blood stages in vitro with low toxicity to host cells. To elucidate its molecular mechanisms, an affinity-based protein profiling (AfBPP) approach was applied to yeast and P. falciparum proteomes. New (pro-) AfBPP probes based on the 3-benz(o)yl-6-fluoro-menadione scaffold were synthesized. With optimized conditions of both photoaffinity labeling and click reaction steps, the AfBPP protocol was then applied to a yeast proteome, yielding 11 putative drug-protein targets. Among these, we found four proteins associated with oxidoreductase activities, the hypothesized type of targets for plasmodione and its metabolites, and other proteins associated with the mitochondria. In Plasmodium parasites, the MS analysis revealed 44 potential plasmodione targets that need to be validated in further studies. Finally, the localization of a 3-benzyl-6-fluoromenadione AfBPP probe was studied in the subcellular structures of the parasite at the trophozoite stage.
PubMed: 38639212
DOI: 10.1002/cbic.202400187 -
RoFo : Fortschritte Auf Dem Gebiete Der... Apr 2024150 years ago, on March 1, 1874, Prof. Dr. Alban Köhler, pioneer in X-ray diagnostics and Co-founder of the German Radiological Society, was born. His memoirs...
150 years ago, on March 1, 1874, Prof. Dr. Alban Köhler, pioneer in X-ray diagnostics and Co-founder of the German Radiological Society, was born. His memoirs "Röntgenarztes Erdenwallen", an extraordinarily personal, interesting and humorous autobiography of a contemporary witness from the early days of the X-ray era, will be used to commemorate him. This work also focuses on his outstanding X-ray books on skeletal diseases and standard variants.
PubMed: 38626883
DOI: 10.1055/a-2284-5540 -
Radiology Apr 2024The diagnosis and management of chronic nonspinal osteomyelitis can be challenging, and guidelines regarding the appropriateness of performing percutaneous image-guided... (Review)
Review
The diagnosis and management of chronic nonspinal osteomyelitis can be challenging, and guidelines regarding the appropriateness of performing percutaneous image-guided biopsies to acquire bone samples for microbiological analysis remain limited. An expert panel convened by the Society of Academic Bone Radiologists developed and endorsed consensus statements on the various indications for percutaneous image-guided biopsies to standardize care and eliminate inconsistencies across institutions. The issued statements pertain to several commonly encountered clinical presentations of chronic osteomyelitis and were supported by a literature review. For most patients, MRI can help guide management and effectively rule out osteomyelitis when performed soon after presentation. Additionally, in the appropriate clinical setting, open wounds such as sinus tracts and ulcers, as well as joint fluid aspirates, can be used for microbiological culture to determine the causative microorganism. If MRI findings are positive, surgery is not needed, and alternative sites for microbiological culture are not available, then percutaneous image-guided biopsies can be performed. The expert panel recommends that antibiotics be avoided or discontinued for an optimal period of 2 weeks prior to a biopsy whenever possible. Patients with extensive necrotic decubitus ulcers or other surgical emergencies should not undergo percutaneous image-guided biopsies but rather should be admitted for surgical debridement and intraoperative cultures. Multidisciplinary discussion and approach are crucial to ensure optimal diagnosis and care of patients diagnosed with chronic osteomyelitis.
Topics: Adult; Humans; Biopsy, Fine-Needle; Osteomyelitis; Inflammation; Anti-Bacterial Agents; Radiologists
PubMed: 38625010
DOI: 10.1148/radiol.231348 -
Nature Communications Apr 2024Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven...
Formation of organo-typical vascular networks requires cross-talk between differentiating parenchymal cells and developing blood vessels. Here we identify a Vegfa driven venous sprouting process involving parenchymal to vein cross-talk regulating venous endothelial Vegfa signaling strength and subsequent formation of a specialized angiogenic cell, prefabricated with an intact lumen and pericyte coverage, termed L-Tip cell. L-Tip cell selection in the venous domain requires genetic interaction between vascular Aplnra and Kdrl in a subset of venous endothelial cells and exposure to parenchymal derived Vegfa and Apelin. Parenchymal Esm1 controls the spatial positioning of venous sprouting by fine-tuning local Vegfa availability. These findings may provide a conceptual framework for understanding how Vegfa generates organo-typical vascular networks based on the selection of competent endothelial cells, induced via spatio-temporal control of endothelial Kdrl signaling strength involving multiple parenchymal derived cues generated in a tissue dependent metabolic context.
Topics: Angiogenesis; Endothelial Cells; Neovascularization, Physiologic; Veins
PubMed: 38600061
DOI: 10.1038/s41467-024-47434-x