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Copyright of Canadian Journal of Pathology is the property of Canadian Association of Pathologists and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The severe form of malaria, i.e., cerebral malaria caused by Plasmodium falciparum, is a complex neurological syndrome. Surviving persons have a risk of behavioral difficulties, cognitive disorders, and epilepsy. Cerebral malaria is associated with multiple organ dysfunctions. The adhesion and accumulation of infected RBCs, platelets, and leucocytes (macrophages, CD4+ and CD8+ T cells, and monocytes) in the brain microvessels play an essential role in disease progression. Micro-vascular hindrance by coagulation and endothelial dysfunction contributes to neurological damage and the severity of the disease. Recent studies in human cerebral malaria and the murine model of cerebral malaria indicate that different pathogens as well as host-derived factors are involved in brain microvessel adhesion and coagulation that induces changes in vascular permeability and impairment of the blood-brain barrier. Efforts to alleviate blood-brain barrier dysfunction and de-sequestering of RBCs could serve as adjunct therapies. In this review, we briefly summarize the current understanding of the pathogenesis of cerebral malaria, the role of some factors (NK cells, platelet, ANG-2/ANG-1 ratio, and PfEMP1) in disease progression and various functions of Mesenchymal stem cells. This review also highlighted the implications of MSCs as a regenerative medicine. [ABSTRACT FROM AUTHOR]

The choanoflagellate Salpingoeca rosetta is a microbial marine eukaryote that can switch between unicellular and multicellular states. As one of the closest living relatives of animals, this organism has become a model for understanding how multicellularity evolved in the animal lineage. Previously our laboratories isolated and synthesized a bacterially produced sulfonolipid that induces S. rosetta to form multicellular "rosettes." In this study, we report the identification of a bacterially produced inhibitor of rosettes (IOR-1) as well as the total synthesis of this molecule and all of its stereoisomers. Our results confirm the previously noted specificity and potency of rosette-modulating molecules, expand our understanding of the complex chemical ecology between choanoflagellates and rosette-inducing bacteria, and provide a synthetic probe template for conducting further mechanistic studies on the emergence of multicellularity.

Strain-transcending antibodies against virulence-associated subsets of P. falciparum -infected erythrocyte surface antigens could protect children from severe malaria. However, the evidence supporting the existence of such antibodies is incomplete and inconsistent. One subset of surface antigens associated with severe malaria, rosette-mediating Plasmodium falciparum Erythrocyte Membrane Protein one (PfEMP1) variants, cause infected erythrocytes to bind to uninfected erythrocytes to form clusters of cells (rosettes) that contribute to microvascular obstruction and pathology. Here, we tested plasma from 80 individuals living in malaria-endemic regions for IgG recognition of the surface of four P. falciparum rosetting strains using flow cytometry. Broadly reactive plasma samples were then used in antibody elution experiments in which intact IgG was eluted from the surface of infected erythrocytes and transferred to heterologous rosetting strains to look for strain-transcending antibodies. We found that seroprevalence (percentage of positive plasma samples) against allopatric rosetting strains was high in adults (63%-93%) but lower in children (13%-48%). Strain-transcending antibodies were present in nine out of eleven eluted antibody experiments, with six of these recognizing multiple heterologous rosetting parasite strains. One eluate had rosette-disrupting activity against heterologous strains, suggesting PfEMP1 as the likely target of the strain-transcending antibodies. Naturally acquired strain-transcending antibodies to rosetting P. falciparum strains in humans have not been directly demonstrated previously. Their existence suggests that such antibodies could play a role in clinical protection and raises the possibility that conserved epitopes recognized by strain-transcending antibodies could be targeted therapeutically by monoclonal antibodies or vaccines., Competing Interests: The authors declare no conflict of interest.

Rosette-forming glioneuronal tumor (RGNT) of the fourth ventricle is a mixed glio-neuronal neoplasm recently codified by the World Health Organization WHO Classification of Central Nervous System (CNS) Tumors (2007). To date, 43 cases have been described in the literature; most occurring in the fourth ventricle region. We report the fourth case involving the pineal region in a 16-year-old female with signs of increased intracranial pressure (ICP). A stereotactic biopsy of the mass was followed by a debulking procedure. Both specimens revealed classic RGNT histology. The patient had stable scans 7 months post-resection. The clinical, radiological and histopathologic features of the previously described 43 cases are reviewed along with our illustrative case. Mean age of patients was 30 ± 12.8 years with 1.9:1 female to male ratio. The most common presenting signs related to increased ICP and posterior fossa involvement, including: headache (62.8%), ataxia (39.5%) and vomiting and vertigo (both 16.3%). This tumor usually presents with cystic changes (54.5%) with focal enhancement (60.9%) and hydrocephalus (43.2%). Microcalcifications and satellite lesions were common radiographic observations. All reported cases had the classic biphasic pattern. Rosenthal fibers and eosinophilic granular bodies are each present in approximately two thirds of cases. Ki-67 labeling index is consistently low (mean (%): 1.8 ± 0.75 SD). The isocitrate dehydrogenase 1 or 2 mutation found in low grade diffuse gliomas is not identified in this RGNT case. Reported outcome is nearly uniformly excellent after complete or subtotal resection. A solitary report of recurrence after 10 years and the limited experience with this entity suggest that long term follow up is advisable.

The article discusses that the morphogenesis of zebrafish posterior lateral line (PLL) is a good predictive model largely used in biology to study cell coordinated reorganization and collective migration regulating pathologies and human embryonic processes. It mentions that cell proliferation and cascade of phenotypic transitions play a fundamental role; and a multiscale hybrid model integrating a discrete approach for the cellular level and a continuous description for the molecular scale.

Copyright of Revue d'Orthopédie Dento-Faciale is the property of Parresia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Infection of asexual stage of the malaria parasite Plasmodium falciparum induce morphologic, functional and antigenic changes in their host erythrocyte membranes. The consequence of these changes is that infected erythrocyte develop the ability to sequester by binding to capyllary endothelial cells, venula and to uninfected erythrocyte is termed rosette formation. Recently, rosette formation be interesting phenomenon because it was presumed imprtant to phatogenesis of severe malaria such as cerebral malaria through sequesteration of parasite in microvasculature. Rossete formation is a binding mechanism between Plasmodium falciparum infected erythrocyte to the normal ones, which involve the role of parasite protein ligands such as PfEMP1 expressed on infected eythrocyte as surface antigen through DBL1-alfa domain that bind to CR-1 receptor and/or A-antigen on the uninfected erythrocyte as target cell. Taking into accounts that all strains of P. falciparum parasite could cause rosette formation, therefore information of rosette formation still needed such as site of sequesteration, identity receptors, haemodinamic enviroment of microvascular and domain mapping on rosette formation to elucidate the role of rosette formation in phatogenesis of severe malaria.

Background: Rosette formation is an unusual finding in malignant lymphomas. We report a case of a diffuse large B-cell lymphoma (DLBCL) with abundant rosette formation histologically mimicking non lymphoid tumors. Case presentation: A sixty-five-year-old female presented with a complaint of swelling on left side axillary region since a period of six months with no history of fever, fatigue or weight loss or other similar swellings elsewhere. No relevant personal and family history relatable to the present complaint. Subsequent clinical and radiological investigations revealed isolated left axillary lymphadenopathy. The lymph node on further biopsy showed a particular morphology of pseudorosette formation masquerading a metastatic rosette forming malignancies. Subsequent histopathological and immunohistochemical investigations revealed a rare morphological variant of diffuse large B cell lymphoma. The fluorodeoxyglucose positron emission tomography scan showed multiple discreet supra-diphramatic (left lower cervical and left axillary lymph nodes) metabolically active lymph nodes. Conclusion: Diffuse large B cell lymphoma with rosette formation is a rare entity which can mimic other tumors with rosette formation in a metastatic node. Knowledge on the rosette forming lymphoma entity is thus essential for diagnosis and treatment plan. To the best of our knowledge this case report is the sixth known documented case of a diffuse large B cell lymphoma with rosette in literature.

Rosette-forming glioneuronal tumor (RGNT) of the 4th ventricle is a newly described WHO grade I brain tumor included in recent WHO classification of CNS tumors. It is a biphasic tumor thought to originate from pluripotent progenitor cells of subependymal plate. Intra-operative diagnosis plays an important role, as complete surgical excision is the treatment of choice. We are reporting a case of RGNT in a 19 years-old young male emphasizing the intra-operative pathological pointers and their role in accurate diagnosis for the suitable surgical intervention.

Human cytomegalovirus (HCMV) is a leading cause of birth defects in humans. These birth defects include microcephaly, sensorineural hearing loss, vision loss, and cognitive impairment. The process by which the developing fetus incurs these neurological defects is poorly understood. To elucidate some of these mechanisms, we have utilized HCMV-infected induced pluripotent stem cells (iPSCs) to generate in vitro brain organoids, modeling the first trimester of fetal brain development. Early during culturing, brain organoids generate neural rosettes. These structures are believed to model neural tube formation. Rosette formation was analyzed in HCMV-infected and mock-infected brain organoids at 17, 24, and 31 days postinfection. Histological analysis revealed fewer neural rosettes in HCMV-infected compared to mock-infected organoids. HCMV-infected organoid rosettes incurred multiple structural deficits, including increased lumen area, decreased ventricular zone depth, and decreased cell count. Immunofluorescent (IF) analysis found that nidogen-1 (NID1) protein expression in the basement membrane surrounding neural rosettes was greatly reduced by virus infection. IF analysis also identified a similar downregulation of laminin in basement membranes of HCMV-infected organoid rosettes. Knockdown of NID1 alone in brain organoids impaired their development, leading to the production of rosettes with increased lumen area, decreased structural integrity, and reduced laminin localization in the basement membrane, paralleling observations in HCMV-infected organoids. Our data strongly suggest that HCMV-induced downregulation of NID1 impairs neural rosette formation and integrity, likely contributing to many of HCMV's most severe birth defects. IMPORTANCE HCMV infection in pregnant women continues to be the leading cause of virus-induced neurologic birth defects. The mechanism through which congenital HCMV (cCMV) infection induces pathological changes to the developing fetal central nervous system (CNS) remains unclear. Our lab previously reproduced identified clinical defects in HCMV-infected infants using a three dimensional (3D) brain organoid model. In this new study, we have striven to discover very early HCMV-induced changes in developing brain organoids. We investigated the development of neural tube-like structures, neural rosettes. HCMV-infected rosettes displayed multiple structural abnormalities and cell loss. HCMV-infected rosettes displayed reduced expression of the key basement membrane protein, NID1. We previously found NID1 to be specifically targeted in HCMV-infected fibroblasts and endothelial cells. Brain organoids generated from NID1 knockdown iPSCs recapitulated the structural defects observed in HCMV-infected rosettes. Findings in this study revealed HCMV infection induced early and dramatic structural changes in 3D brain organoids. We believe our results suggest a major role for infection-induced NID1 downregulation in HCMV-induced CNS birth defects., Competing Interests: The authors declare no conflict of interest.

A hallmark of gastrulation is the establishment of germ layers by internalization of cells initially on the exterior. In C. elegans the end of gastrulation is marked by the closure of the ventral cleft, a structure formed as cells internalize during gastrulation, and the subsequent rearrangement of adjacent neuroblasts that remain on the surface. We found that a nonsense allele of srgp-1/srGAP leads to 10-15% cleft closure failure. Deletion of the SRGP-1/srGAP C-terminal domain led to a comparable rate of cleft closure failure, whereas deletion of the N-terminal F-BAR region resulted in milder defects. Loss of the SRGP-1/srGAP C-terminus or F-BAR domain results in defects in rosette formation and defective clustering of HMP-1/⍺-catenin in surface cells during cleft closure. A mutant form of HMP-1/⍺-catenin with an open M domain can suppress cleft closure defects in srgp-1 mutant backgrounds, suggesting that this mutation acts as a gain-of-function allele. Since SRGP-1 binding to HMP-1/⍺-catenin is not favored in this case, we sought another HMP-1 interactor that might be recruited when HMP-1/⍺-catenin is constitutively open. A good candidate is AFD-1/afadin, which genetically interacts with cadherin-based adhesion later during embryonic elongation. AFD-1/afadin is prominently expressed at the vertex of neuroblast rosettes in wildtype, and depletion of AFD-1/afadin increases cleft closure defects in srgp-1/srGAP and hmp-1R551/554A/⍺-catenin backgrounds. We propose that SRGP-1/srGAP promotes nascent junction formation in rosettes; as junctions mature and sustain higher levels of tension, the M domain of HMP-1/⍺-catenin opens, allowing maturing junctions to transition from recruitment of SRGP-1/srGAP to AFD-1/afadin. Our work identifies new roles for ⍺-catenin interactors during a process crucial to metazoan development., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Serre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The occurrence impacted teeth, single or multiple is very common. But, phenomenon of kissing molars is an extremely rare phenomenon. Mandibular third molars are the most common impacted teeth. Mandibular first or second molars does not share the same frequency of occurrence. But, there are rare cases in which the occlusal surfaces of impacted molars are united by the same follicular space and the roots point in the opposite direction, and are termed as kissing molars. Sometimes, these teeth will be associated with pathologies. This article reports a rare case of mandibular bilateral kissing molars.

Se realizó el estudio descriptivo de algunas variables de la inmunidad celular y humoral que incluyen las rosetas espontáneas y activas, las inmunoglobulinas, el complemento hemolítico total y los inmunocomplejos circulantes, en 30 pacientes politraumatizados atendidos en la unidad de terapia intensiva del Instituto Superior de Medicina Militar "Dr. Luis Díaz Soto". Los pacientes fueron monitoreados mediante 3 extracciones de sangre que correspondieron a las 24 h, a las 72 h y a los 7 d después de haber sufrido el trauma. Se produjo una disminución de las rosetas, cambios de los valores de inmunoglobulinas y aumento de los inmunocomplejos circulantes; por lo que el seguimiento de estas variables sería importante en la evaluación de los politraumatizadosThe descriptive study of some cell and humoral immunity variables including spontaneous and active rosettes, immunoglobulins, total hemolytic complement and circulating immunocomplexes was carried in 30 multiple trauma patients seen at the intensive care unit of "Dr Luis Díaz Soto" Higher Institute of Military Medicine. Patients were monitored by means of three blood extractions taken 24 h, 72h and 7 days after their having suffered the trauma. There was a reduction in rosettes, changes in the immunoglobulin values and an increase of circulating immunocomplexes, hence the follow-up of these variables would be important for the assessment of multiple trauma patients

Plasmodium vivax is a public health problem and the most common type of malaria outside sub-Saharan Africa. The capacity of cytoadhesion, rosetting, and liver latent phase development could impact treatment and disease control. Although the ability to P. vivax gametocyte develop rosetting is known, it is not yet clear which role it plays during the infection and transmission process to the mosquito. Here, we used ex vivo approaches for evaluate the rosetting P. vivax gametocytes capacity and we have investigated the effect of this adhesive phenotype on the infection process in the vector Anopheles aquasalis mosquito. Rosette assays were performed in 107 isolates, and we have observed an elevated frequency of cytoadhesive phenomena (77,6%). The isolates with more than 10% of rosettes have presented a higher infection rate in Anopheles aquasalis (p=0.0252). Moreover, we found a positive correlation between the frequency of parasites in rosetting with the infection rate (p=0.0017) and intensity (p=0.0387) in the mosquito. The disruption of P. vivax rosette formation through mechanical rupture assay confirmed the previously findings, since the paired comparison showed that isolates with disrupted rosettes have a lower infection rate (p<0.0001) and intensity (p=0.0003) compared to the control group (no disruption). Herein we have demonstrated for the first time a potential effect of the rosette phenomenon on the infection process in the mosquito vector An. aquasalis , favoring its capacity and intensity of infection, thus allowing the perpetuation of the parasite cycle life., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Salazar Alvarez, Carneiro Barbosa, Vera Lizcano, Baia da Silva, Gonçalves Santana, Fabbri, Paoluci Pimenta, Monteiro, Albrecht, Guimarães de Lacerda, Trindade Maranhão Costa and Costa Pinto Lopes.)

Surface colonization is characteristic for a broad range of marine roseobacters and many strains have been isolated from biofilms, microbial mats and dinoflagellates. Phaeobacter inhibens DSM 17395, one of the best-studied representatives of the Roseobacter group, is an effective colonizer of marine surfaces, but the genetic basis of this trait is unknown. Based on the composition of its 65-kb RepA-I type plasmid that contains more than 20 genes for polysaccharide metabolism, including a rhamnose operon, which is required for O-antigen formation in Escherichia coli , it was hypothesized that this replicon was essential for surface attachment. Accordingly, a holistic approach was taken and the functional role of this extrachromosomal element in P. inhibens was investigated. Plasmid curing was performed with the homologous RepA-I replication system of Dinoroseobacter shibae DSM 16493 T . The Δ65-kb mutant completely lost its stickiness and could neither attach to artificial (glass, polystyrene) nor to natural surfaces (algae) and, consequently, its ability to form biofilms was impaired. Surprisingly, the mutant also lost the capacity for flagellar swimming motility required for surface colonization and the dispersal of biofilms. The data clearly showed that the 65-kb replicon of P. inhibens DSM 17395 was a genuine biofilm plasmid-mediating surface attachment. Homologous replicons are widely distributed among Rhodobacterales thus indicating the general importance of extrachromosomal elements for biofilm formation. [ABSTRACT FROM AUTHOR]