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PLoS Pathogens May 2024Ilarviruses are a relatively understudied but important group of plant RNA viruses that includes a number of crop pathogens. Their genomes comprise three RNA segments...
Ilarviruses are a relatively understudied but important group of plant RNA viruses that includes a number of crop pathogens. Their genomes comprise three RNA segments encoding two replicase subunits, movement protein, coat protein (CP), and (in some ilarvirus subgroups) a protein that suppresses RNA silencing. Here we report that, in many ilarviruses, RNA3 encodes an additional protein (termed CP-RT) as a result of ribosomal readthrough of the CP stop codon into a short downstream readthrough (RT) ORF. Using asparagus virus 2 as a model, we find that CP-RT is expressed in planta where it functions as a weak suppressor of RNA silencing. CP-RT expression is essential for persistent systemic infection in leaves and shoot apical meristem. CP-RT function is dependent on a putative zinc-finger motif within RT. Replacing the asparagus virus 2 RT with the RT of an ilarvirus from a different subgroup restored the ability to establish persistent infection. These findings open up a new avenue for research on ilarvirus silencing suppression, persistent meristem invasion and vertical transmission.
PubMed: 38814986
DOI: 10.1371/journal.ppat.1012034 -
Frontiers in Veterinary Science 2024This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The...
This report describes a case of transmural migration of a gossypiboma from the peritoneum into the urinary bladder in a 4-year-old, female spayed, mixed-breed dog. The dog was presented on an emergency basis for complete urethral obstruction with radiographic evidence of urocystolithiasis. An exploratory laparotomy was performed and a 4-5 cm mass was identified which was confluent with the apex of the urinary bladder. The mass and bladder were exteriorized and isolated, and an apical, partial cystectomy was performed to remove the mass and gain access to the uroliths within the lumen of the bladder. A 4×4 surgical sponge was identified within the trigone of the bladder, it had multiple uroliths; another sponge was also found within the mass itself. This case demonstrates an atypical cause of urethral obstruction and serves as the first reported case of transmural migration of a gossypiboma into the urinary bladder of a dog. It also illustrates the importance of establishing routine operating procedures including gauze counts and the use of radiopaque-labeled surgical gauze.
PubMed: 38812558
DOI: 10.3389/fvets.2024.1394052 -
Frontiers in Bioscience (Landmark... May 2024Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we...
AIMS
Changes in myocardial mitochondrial morphology and function in premature ventricular contractions (PVCs)-induced cardiomyopathy (PVCCM) remain poorly studied. Here, we investigated the effects of PVCs with different coupling intervals (CIs) on myocardial mitochondrial remodelling in a canine model of PVCCM.
METHODS AND RESULTS
Twenty-one beagles underwent pacemaker implantation and were randomised into the sham (n = 7), short-coupled PVCs (SCP, n = 7), and long-coupled PVCs (LCP, n = 7) groups. Right ventricular (RV) apical bigeminy was produced for 12-week to induce PVCCM in the SCP (CI, 250 ms) and LCP (CI, 350 ms) groups. Echocardiography was performed at baseline and biweekly thereafter to evaluate cardiac function. Masson's trichrome staining measured ventricular interstitial fibrosis. The ultrastructural morphology of the myocardial mitochondria was analysed using transmission electron microscopy. Mitochondrial Ca2+ concentration, reactive oxygen species (ROS) levels, adenosine triphosphate (ATP) content, membrane potential, and electron transport chain (ETC) complex activity were measured to assess myocardial mitochondrial function. Twelve-week-PVCs led to left ventricular (LV) enlargement with systolic dysfunction, disrupted mitochondrial morphology, increased mitochondrial Ca2+ concentration and ROS levels, decreased mitochondrial ATP content and membrane potential, and impaired ETC complex activity in both the SCP and LCP groups (all < 0.01 the sham group). Ventricular fibrosis was observed only in canines with LCP. Worse cardiac function and more pronounced abnormalities in mitochondrial morphology and function were observed in the LCP group than to the SCP group (all < 0.05).
CONCLUSION
We demonstrated myocardial mitochondrial abnormalities in dogs with PVCCM, characterised by abnormal mitochondrial morphology, mitochondrial Ca2+ overload, oxidative stress, and impaired mitochondrial energy metabolism. Compared to SCP, long-term LCP exposure resulted in more severe mitochondrial remodelling and cardiac dysfunction in dogs.
Topics: Animals; Dogs; Mitochondria, Heart; Cardiomyopathies; Disease Models, Animal; Ventricular Premature Complexes; Reactive Oxygen Species; Calcium; Male; Adenosine Triphosphate; Membrane Potential, Mitochondrial; Echocardiography
PubMed: 38812311
DOI: 10.31083/j.fbl2905200 -
ELife May 2024Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called the hemogenic endothelium (HE). The HE appears to give birth to cells of different...
Hematopoietic stem cells emerge in the embryo from an aortic-derived tissue called the hemogenic endothelium (HE). The HE appears to give birth to cells of different nature and fate but the molecular principles underlying this complexity are largely unknown. Here we show, in the zebrafish embryo, that two cell types emerge from the aortic floor with radically different morphodynamics. With the support of live imaging, we bring evidence suggesting that the mechanics underlying the two emergence types rely, or not, on apicobasal polarity establishment. While the first type is characterized by reinforcement of apicobasal polarity and maintenance of the apical/luminal membrane until release, the second type emerges via a dynamic process reminiscent of trans-endothelial migration. Interfering with Runx1 function suggests that the balance between the two emergence types depends on tuning apicobasal polarity at the level of the HE. In support of this and unexpectedly, we show that Pard3ba - one of the four Pard3 proteins expressed in the zebrafish - is sensitive to interference with Runx1 activity, in aortic endothelial cells. This supports the idea of a signaling cross talk controlling cell polarity and its associated features, between aortic and hemogenic cells. In addition, using new transgenic fish lines that express Junctional Adhesion Molecules and functional interference, we bring evidence for the essential role of ArhGEF11/PDZ-RhoGEF in controlling the HE-endothelial cell dynamic interface, including cell-cell intercalation, which is ultimately required for emergence completion. Overall, we highlight critical cellular and dynamic events of the endothelial-to-hematopoietic transition that support emergence complexity, with a potential impact on cell fate.
Topics: Zebrafish; Animals; Zebrafish Proteins; Cell Polarity; Core Binding Factor Alpha 2 Subunit; Hematopoietic Stem Cells; Hemangioblasts; Embryo, Nonmammalian; Animals, Genetically Modified
PubMed: 38809590
DOI: 10.7554/eLife.91429 -
The Journal of Innovations in Cardiac... May 2024A 78-year-old male patient with complete atrioventricular block underwent an uncomplicated pacemaker implantation. After 24 h, he presented acute chest pain, dyspnea,...
A 78-year-old male patient with complete atrioventricular block underwent an uncomplicated pacemaker implantation. After 24 h, he presented acute chest pain, dyspnea, ST-segment-elevation in the anterior leads, left ventricular apical ballooning, and an ejection fraction of 35%. His coronary angiogram was normal. Within 2 days, his symptoms and electrocardiogram (ECG) abnormalities disappeared, while wall motion abnormalities recovered after 6 weeks. A diagnosis of takotsubo syndrome (TTS) was made. Pacemaker implantation has been described as a potential trigger for TTS. The clinical picture exhibits some peculiarities, including a higher percentage of men and asymptomatic patients and challenging ST-segment interpretation of paced ECGs. It is unclear whether pathophysiologic mechanisms are different compared to other forms of TTS and whether the acute initiation of ventricular pacing plays a role.
PubMed: 38808172
DOI: 10.19102/icrm.2024.15051 -
Frontiers in Cellular and Infection... 2024Diversity in malarial antigens is an immune evasion mechanism that gives malaria parasites an edge over the host. Immune responses against one variant of a polymorphic...
INTRODUCTION
Diversity in malarial antigens is an immune evasion mechanism that gives malaria parasites an edge over the host. Immune responses against one variant of a polymorphic antigen are usually not fully effective against other variants due to altered epitopes. This study aimed to evaluate diversity in the Plasmodium falciparum antigens apical membrane antigen 1 (PfAMA1) and circumsporozoite protein (PfCSP) from circulating parasites in a malaria-endemic community in southern Ghana and to determine the effects of polymorphisms on antibody response specificity.
METHODS
The study involved 300 subjects, whose infection status was determined by microscopy and PCR. Diversity within the two antigens was evaluated by msp2 gene typing and molecular gene sequencing, while the host plasma levels of antibodies against PfAMA1, PfCSP, and two synthetic 24mer peptides from the conserved central repeat region of PfCSP, were measured by ELISA.
RESULTS
Of the 300 subjects, 171 (57%) had infection, with 165 of the 171 (96.5%) being positive for either or both of the allelic families. Gene sequencing of DNA from 55 clonally infected samples identified a total of 56 non-synonymous single nucleotide polymorphisms (SNPs) for the gene and these resulted in 44 polymorphic positions, including two novel positions (363 and 365). Sequencing of the Pfcsp gene from 69 clonal DNA samples identified 50 non-synonymous SNPs that resulted in 42 polymorphic positions, with half (21) of these polymorphic positions being novel. Of the measured antibodies, only anti-PfCSP antibodies varied considerably between PCR parasite-positive and parasite-negative persons.
DISCUSSION
These data confirm the presence of a considerable amount of unique, previously unreported amino acid changes, especially within PfCSP. Drivers for this diversity in the Pfcsp gene do not immediately seem apparent, as immune pressure will be expected to drive a similar level of diversity in the gene.
Topics: Plasmodium falciparum; Antigens, Protozoan; Ghana; Humans; Protozoan Proteins; Malaria, Falciparum; Membrane Proteins; Antibodies, Protozoan; Female; Adult; Male; Adolescent; Young Adult; Child; Genetic Variation; Child, Preschool; Middle Aged; Sequence Analysis, DNA; Enzyme-Linked Immunosorbent Assay; Polymerase Chain Reaction; Antigenic Variation; DNA, Protozoan
PubMed: 38808064
DOI: 10.3389/fcimb.2024.1375249 -
Cureus Apr 2024Radicular cysts are the most common forms of cysts in the jaws. They develop from epithelial residues in the periodontal ligament in response to periapical infection...
Radicular cysts are the most common forms of cysts in the jaws. They develop from epithelial residues in the periodontal ligament in response to periapical infection following pulpal necrosis. This condition is typically asymptomatic and mostly affects the tooth's apices. It primarily affects non-vital teeth and is characterized by inflammation. Cyst development is the final stage of the inflammatory process after a periapical infection; hence, it often occurs later in life. A cyst in the maxilla can occasionally spread across the maxillary sinus. Radicular cysts can be treated with surgical endodontics, the removal of the problematic tooth, enucleation with primary closure, or marsupialization and enucleation. This case report discusses a successful surgical therapy for an infected radicular cyst.
PubMed: 38807828
DOI: 10.7759/cureus.59216 -
Scientific Reports May 2024Sex hormones affect structural and functional plasticity in the rodent hippocampus. However, hormone levels not only differ between males and females, but also fluctuate...
Sex hormones affect structural and functional plasticity in the rodent hippocampus. However, hormone levels not only differ between males and females, but also fluctuate across the female estrous cycle. While sex- and cycle-dependent differences in dendritic spine density and morphology have been found in the rodent CA1 region, but not in the CA3 or the dentate gyrus, comparable structural data on CA2, i.e. the hippocampal region involved in social recognition memory, is so far lacking. In this study, we, therefore, used wildtype male and female mice in diestrus or proestrus to analyze spines on dendritic segments from identified CA2 neurons. In basal stratum oriens, we found no differences in spine density, but a significant shift towards larger spine head areas in male mice compared to females. Conversely, in apical stratum radiatum diestrus females had a significantly higher spine density, and females in either cycle stage had a significant shift towards larger spine head areas as compared to males, with diestrus females showing the larger shift. Our results provide further evidence for the sexual dimorphism of hippocampal area CA2, and underscore the importance of considering not only the sex, but also the stage of the estrous cycle when interpreting morphological data.
Topics: Animals; Male; Female; Dendritic Spines; Mice; Estrous Cycle; CA2 Region, Hippocampal; Sex Characteristics; Neurons
PubMed: 38806649
DOI: 10.1038/s41598-024-62951-x -
Endocrinology, Diabetes & Metabolism... Apr 2024RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented...
SUMMARY
RET mutations are implicated in 60% of medullary thyroid cancer (MTC) cases. The RET-selective tyrosine kinase inhibitor selpercatinib is associated with unprecedented efficacy compared to previous multi-kinase treatments. Langerhans cell histiocytosis (LCH) is a clonal histiocytic neoplasm usually driven by somatic BRAF mutations, resulting in dysregulated MAPK signalling. We describe a 22-year-old woman with metastatic MTC to regional lymph nodes, lung and liver. Tumour tissue harboured a somatic pathogenic RET variant p.(M918T) and selpercatinib was commenced. She experienced sustained clinical, biochemical and radiological responses. Two years later, she developed rapidly progressive apical lung nodules, prompting biopsy. Histopathology demonstrated LCH with a rare BRAF variant p.(V600_K601>D). The lung nodules improved with inhaled corticosteroids. We hypothesize that selective pressure from RET blockade may have activated a downstream somatic BRAF mutation, resulting in pulmonary LCH. We recommend continued vigilance for neoplasms driven by dysregulated downstream MAPK signalling in patients undergoing selective RET inhibition.
LEARNING POINTS
Patients with RET-altered MTC can experience rapid disease improvement and sustained disease stability with selective RET blockade (selpercatinib). LCH is a clonal neoplasm driven by MAPK activation, for which the most common mechanism is BRAF mutation. Both MTC and pulmonary LCH are driven by dysregulated MAPK signalling pathway activation. We hypothesise that the RET-specific inhibitor selpercatinib may have caused the activation of dormant LCH secondary to selective pressure and clonal proliferation.
PubMed: 38804700
DOI: 10.1530/EDM-23-0079 -
European Journal of Paediatric Dentistry May 2024Dilaceration can lead to impaction of maxillary incisors, resulting in both aesthetic and functional problems. This case report presents the multidisciplinary approach...
BACKGROUND
Dilaceration can lead to impaction of maxillary incisors, resulting in both aesthetic and functional problems. This case report presents the multidisciplinary approach to managing an inverse impacted dilacerated left lateral incisor in a 9-year-old male patient.
CASE REPORT
The orthodontic alignment of the remaining three incisors was achieved within six months. After using the diode laser to remove the gingiva covering the right lateral incisor during alignment process, a lingual button was bonded. The primary left canine and the impacted permanent left lateral incisor were extracted by raising the full-thickness mucoperiosteal flap, followed by the transplantation of the dilacerated lateral incisor into its correct position, splinted to the adjacent central incisors using composite resin. Root canal treatment was performed after the apical plug was created with mineral trioxide aggregate. The composite splint was removed after three weeks, and a new bracket was bonded to the left lateral incisor. It was left passively for 18 months until the permanent canines started to erupt. Light orthodontic forces were then applied for six months, and a passive eruption was expected over three months to properly position the canines within the dental arch. After an 11-year follow-up, the incisor displayed no clinical symptoms, although radiographic examination revealed external resorption in the long-term.
CONCLUSION
This case demonstrates the successful and fast autotransplantation of an immature inverse impacted dilacerated incisor, highlighting the long-term clinical success and favorable aesthetic outcomes.
Topics: Humans; Male; Child; Incisor; Tooth, Impacted; Follow-Up Studies; Transplantation, Autologous; Root Canal Therapy; Maxilla; Composite Resins; Lasers, Semiconductor; Cuspid; Calcium Compounds; Oxides; Drug Combinations; Aluminum Compounds; Silicates
PubMed: 38804663
DOI: 10.23804/ejpd.2024.2017