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Organ sizes and shapes are highly reproducible, or robust, within a species and individuals. Arabidopsis thaliana sepals, which are the leaf-like organs that enclose flower buds, have consistent size and shape, indicating robust development. Cell growth is locally heterogeneous due to intrinsic and extrinsic noise. To achieve robust organ shape, fluctuations in cell growth must average to an even growth rate, which requires that fluctuations are uncorrelated or anticorrelated in time and space. Here, we live image and quantify the development of sepals with an increased or decreased number of cell divisions (lgo mutant and LGO overexpression, respectively), a mutant with altered cell growth variability (ftsh4), and double mutants combining these. Changes in the number of cell divisions do not change the overall growth pattern. By contrast, in ftsh4 mutants, cell growth accumulates in patches of over- and undergrowth owing to correlations that impair averaging, resulting in increased organ shape variability. Thus, we demonstrate in vivo that the number of cell divisions does not affect averaging of cell growth, preserving robust organ morphogenesis, whereas correlated growth fluctuations impair averaging. [ABSTRACT FROM AUTHOR]

BACKGROUND: Undifferentiated carcinomas of the pancreas with osteoclast-like giant cells (UCPOGC) are rare pancreatic neoplasms that account for less than 1% of all pancreatic malignancies. This case report of a 54-year-old male with metastatic UCPOGC adds to the existing literature and further ascertains the clinical and imaging features, treatment options, and prognosis of this rare entity. CASE PRESENTATION: We present the detailed clinical course of a 54-year-old Asian male patient with UCPOGC, with focus on the relevant clinical features and imaging findings that are characteristic of this disease entity. CONCLUSIONS: UCPOGC is an extremely rare pancreatic tumor with a unique histopathology and clinical course. It is often difficult to distinguish UCPOGCs from other pancreatic tumors, such as traditional pancreatic ductal adenocarcinomas (PDAC), on imaging, and it therefore remains a pathological diagnosis. Surgery is generally regarded as the first-line treatment option, and the roles of chemotherapy and radiation are unclear. Due to the exceeding rarity of this tumor, large-scale clinical studies are not feasible. Therefore, it is important to share individual insights and experiences to improve our understanding and care for patients with this devastating disease.

The presence of syncytial-type multinucleated giant tumor cells with emperipolesis in clear cell renal cell carcinoma (RCC) is uncommon, with only 31 cumulative published cases to date. After a rereview of 125 clear cell RCC of World Health Organization/International Society of Urological Pathology grade 3 or 4, 14 clear cell RCCs with admixed syncytial-type giant cells (to our knowledge, the largest series to date) were found with a mean patient age of 67 years and with no sex difference (M = 7, F = 7). Mean tumor size was 7.3 cm. The syncytial-type giant cells comprised between 2% and 20% of the tumor and were present mainly around areas of necrosis. Five tumors were staged as pT1 or pT2, 8 as pT3, and 1 as pT4. Other findings included sarcomatoid differentiation (3/14), rhabdoid differentiation (4/14), and emperipolesis (12/14). Positive immunostains included keratin AE1/AE3 (13/13), carbonic anhydrase 9 and CD10 (12/14 each), vimentin (8/14), EMA (5/12), and alpha-methyacyl-CoA racemase (3/12). Keratin 7, keratin 20, human melanoma black 45, KIT, TFE3, cathepsin K, CD68, CD61, and beta human chorionic gonadotropin were negative. Six of 13 patients had recurrence or metastases during a mean follow-up time of 56 months. Four of 13 patients died of disease, 2 of 13 patients were alive with the disease, and 7 of 13 patients had no evidence of disease. Although the incidence of finding syncytial-type multinucleated giant tumor cells in clear cell RCC is low (approximately 1.2%), given that a subset of the patients showed poor outcomes while lacking other poor histologic parameters (eg, sarcomatoid or rhabdoid differentiation), it may be prudent to recognize and report this feature when encountered. [ABSTRACT FROM AUTHOR]

Root-knot nematodes are polyphagous parasitic nematodes that cause severe losses in the agriculture worldwide. They enter the root in the elongation zone and subtly migrate to the root meristem where they reach the vascular cylinder and establish a feeding site called gall. Inside the galls they induce a group of transfer cells that serve to nurture them along their parasitic stage, the giant cells. Galls and giant cells develop through a process of post-embryogenic organogenesis that involves manipulating different genetic regulatory networks within the cells, some of them through hijacking some molecular transducers of established plant developmental processes, such as lateral root formation or root regeneration. Galls/giant cells formation involves different mechanisms orchestrated by the nematode's effectors that generate diverse plant responses in different plant tissues, some of them include sophisticated mechanisms to overcome plant defenses. Yet, the plant-nematode interaction is normally accompanied to dramatic transcriptomic changes within the galls and giant cells. It is therefore expected a key regulatory role of plant-transcription factors, coordinating both, the new organogenesis process induced by the RKNs and the plant response against the nematode. Knowing the role of plant-transcription factors participating in this process becomes essential for a clear understanding of the plant-RKNs interaction and provides an opportunity for the future development and design of directed control strategies. In this review, we present the existing knowledge of the TFs with a functional role in the plant-RKN interaction through a comprehensive analysis of current scientific literature and available transcriptomic data. [ABSTRACT FROM AUTHOR]

Objectives Cytology reports of metaplastic breast carcinoma (MBC) are rare and limited to short series and simple case reports. To adapt cytology diagnostic criteria to the most recent fifth edition of the World Health Organization Classification of Breast Tumours from 2019, we have reviewed our series from the files of the Institut Curie. Methods A cohort of 66 female patients investigated by cytology with corresponding histologic diagnosis of MBC was identified. Eight cytologic characteristics were analyzed: cellularity, adenocarcinoma cells, squamous cells, spindle cells, giant cells, cytonuclear atypia, necrosis, and osseous/chondroid matrix and compared with histology. Results Cytologic diagnoses were malignant in 58 (88%) cases (of which 29 cases were typed cytologically as MBC), suspicious in 6 (9%) cases, and nondiagnostic in 2 (3%) cases. None of the cytologic examinations was a benign diagnosis. Low-grade adenosquamous carcinoma and fibromatosis-like metaplastic carcinoma exhibited a low degree of cellular atypia. Fibromatosis-like metaplastic carcinoma and spindle cell carcinoma (SpCC) presented spindle cells, while SpCC also demonstrated varying degrees of atypia, the presence of giant cells, and necrosis. Squamous cell carcinoma was characterized by the presence of squamous cells, and metaplastic carcinoma with osseous/chondroid differentiation displayed an osseous/chondroid matrix. Conclusions Fine-needle aspiration holds considerable potential as a valid, independent, and complementary approach to histologic examination of MBC. [ABSTRACT FROM AUTHOR]

Root-knot nematodes(Meloidogyne spp.)are obligate endoparasitic nematodes with features of wide distribution, various hosts, and serious harm. It causes huge economic losses to crops annually, and is one of the most harmful nematodes on crops. When infecting plant root systems, root-knot nematodes induce the re-differentiation of vascular cells at the root tips into multinucleate giant cells, which serve as feeding sites and sole source of nutrients for the nematodes. These cells become the sole source of nutrients for the growth and development of the nematodes. Forming and maintaining ning giant cells are crucial for the growth and reproduction of the nematode. Based on forming of the giant cells and their regulatory mechanisms induced by root-knot nematodes, this paper focuses on the structure of giant cells, cell cycle changes during giant cell formation, nutrient transport, hormone regulation, and the recognition, defense and expression patterns of host plants, and discuses the functions of root-knot nematode effector proteins in the process of giant cell formation. Through the review of the multi-level research progress on the formation and regulation mechanism of giant cells and the molecular mechanism of nematode-plant interaction, it sheds light on the pathogenic mechanisms of root-knot nematodes, aiming to inspire innovative strategies for future research and control of these nematodes. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma multiforme (GBM) ranks as the most frequent form of primary malignant brain tumor. The prognosis for individuals diagnosed with this disease typically leads to a median survival of under two years. Here, we developed mouse models to better understand the genetic basis of GBM, a highly aggressive brain tumor. We found that certain genetic alterations, such as Kirsten rat sarcoma viral oncogene homologue (KRAS) activation and p53 deficiency, cooperate to initiate glioma tumorigenesis. Combining these alterations with adenomatous polyposis coli (APC) haploinsufficiency led to the rapid progression of GBM in the mice, resembling the human disease. These models are valuable for identifying early disease biomarkers and may offer insights for improving the diagnosis and treatment of this challenging brain tumor. Glioblastoma multiforme (GBM) is the most common and deadly type of brain tumor originating from glial cells. Despite decades of clinical trials and research, there has been limited success in improving survival rates. However, molecular pathology studies have provided a detailed understanding of the genetic alterations associated with the formation and progression of glioblastoma—such as Kirsten rat sarcoma viral oncogene homolog (KRAS) signaling activation (5%), P53 mutations (25%), and adenomatous polyposis coli (APC) alterations (2%)—laying the groundwork for further investigation into the biological and biochemical basis of this malignancy. These analyses have been crucial in revealing the sequential appearance of specific genetic lesions at distinct histopathological stages during the development of GBM. To further explore the pathogenesis and progression of glioblastoma, here, we developed the glial-fibrillary-acidic-protein (GFAP)-Cre-driven mouse model and demonstrated that activated KRAS and p53 deficiencies play distinct and cooperative roles in initiating glioma tumorigenesis. Additionally, the combination of APC haploinsufficiency with mutant Kras activation and p53 deletion resulted in the rapid progression of GBM, characterized by perivascular inflammation, large necrotic areas, and multinucleated giant cells. Consequently, our GBM models have proven to be invaluable resources for identifying early disease biomarkers in glioblastoma, as they closely mimic the human disease. The insights gained from these models may pave the way for potential advancements in the diagnosis and treatment of this challenging brain tumor. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide OBJECTIVES The goal of this histological study was to assess the biocompatibility of vascular patches used in the repair of congenital heart defects. METHODS We examined tissue-engineered bovine (n = 7) and equine (n = 7) patches and autologous human pericardium (n = 7), all explanted due to functional issues or follow-up procedures. Techniques like Movat-Verhoeff, von Kossa and immunohistochemical staining were used to analyse tissue composition, detect calcifications and identify immune cells. A semi-quantitative scoring system was implemented to evaluate the biocompatibility aspects, thrombus formation, extent of pannus, inflammation of pannus, cellular response to patch material, patch degradation, calcification and neoadventitial inflammation. RESULTS We observed distinct material degradation patterns among types of patches. Bovine patches showed collagen disintegration and exudate accumulation, whereas equine patches displayed edematous swelling and material dissolution. Biocompatibility scores were lower in terms of cellular response, degradation and overall score for human autologous pericardial patches compared to tissue-engineered types. The extent of pannus formation was not influenced by the type of patch. Bovine patches had notable calcifications causing tissue hardening, and foreign body giant cells were more frequently seen in equine patches. Plasma cells were frequently detected in the neointimal tissue of engineered patches. CONCLUSIONS Our results confirm the superior biocompatibility of human autologous patches and highlight discernible variations in the changes of patch material and the cellular response to patch material between bovine and equine patches. Our approach implements the semi-quantitative scoring of various aspects of biocompatibility, facilitating a comparative quantitative analysis across all types of patches, despite their inherent differences. [ABSTRACT FROM AUTHOR]

Giant cell myositis (GCM) is a rare inflammatory myopathy associated with myasthenia gravis and thymoma. Here, we report on a woman in her late 50s with a history of myasthenia gravis, systemic lupus erythematosus and stage IV thymoma with pleural metastases, who presented with proximal weakness, neuromuscular respiratory failure and hypercalcaemia. She was diagnosed with GCM via muscle biopsy and screened for myocarditis but showed no evidence of myocardial involvement. Her hypercalcaemia was consistent with a granulomatous process, likely driven by her GCM. Her strength gradually improved, and her hypercalcaemia did not recur after treatment with high dose steroids, intravenous immune globulin and plasma exchange. Her course was complicated by several opportunistic infections in the setting of her immunosuppression. Despite the high morbidity associated with GCM, she demonstrated clinical improvement after initiating immunosuppressive therapy and continues to be managed in the outpatient setting.

Summary: The establishment of root‐knot nematode (RKN; Meloidogyne spp.) induced galls in the plant host roots likely involves a wound‐induced regeneration response. Confocal imaging demonstrates physical stress or injury caused by RKN infection during parasitism in the model host Arabidopsis thaliana.The ERF115‐PAT1 heterodimeric transcription factor complex plays a recognized role in wound‐induced regeneration. ERF115 and PAT1 expression flanks injured gall cells likely driving mechanisms of wound healing, implying a local reactivation of cell division which is also hypothetically involved in gall genesis.Herein, functional investigation revealed that ectopic ERF115 expression resulted in premature induction of galls, and callus formation adjacent to the expanding female RKN was seen upon PAT1 upregulation. Smaller galls and less reproduction were observed in ERF115 and PAT1 knockouts. Investigation of components in the ERF115 network upon overexpression and knockdown by qRT‐PCR suggests it contributes to steer gall wound‐sensing and subsequent competence for tissue regeneration. High expression of CYCD6;1 was detected in galls, and WIND1 overexpression resulted in similar ERF115OE gall phenotypes, also showing faster gall induction.Along these lines, we show that the ERF115‐PAT1 complex likely coordinates stress signalling with tissue healing, keeping the gall functional until maturation and nematode reproduction. [ABSTRACT FROM AUTHOR]

Copyright of Die Pathologie is the property of Springer Nature 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.)

Root-knot nematodes are polyphagous parasitic nematodes that cause severe losses in the agriculture worldwide. They enter the root in the elongation zone and subtly migrate to the root meristem where they reach the vascular cylinder and establish a feeding site called gall. Inside the galls they induce a group of transfer cells that serve to nurture them along their parasitic stage, the giant cells. Galls and giant cells develop through a process of post-embryogenic organogenesis that involves manipulating different genetic regulatory networks within the cells, some of them through hijacking some molecular transducers of established plant developmental processes, such as lateral root formation or root regeneration. Galls/giant cells formation involves different mechanisms orchestrated by the nematode´s effectors that generate diverse plant responses in different plant tissues, some of them include sophisticated mechanisms to overcome plant defenses. Yet, the plant-nematode interaction is normally accompanied to dramatic transcriptomic changes within the galls and giant cells. It is therefore expected a key regulatory role of plant-transcription factors, coordinating both, the new organogenesis process induced by the RKNs and the plant response against the nematode. Knowing the role of plant-transcription factors participating in this process becomes essential for a clear understanding of the plant-RKNs interaction and provides an opportunity for the future development and design of directed control strategies. In this review, we present the existing knowledge of the TFs with a functional role in the plant-RKN interaction through a comprehensive analysis of current scientific literature and available transcriptomic data.

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco 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.)

Syncytium formation, i.e., cell-cell fusion resulting in the formation of multinucleated cells, is a hallmark of infection by paramyxoviruses and other pathogenic viruses. This natural mechanism has historically been a diagnostic marker for paramyxovirus infection in vivo and is now widely used for the study of virus-induced membrane fusion in vitro. However, the role of syncytium formation in within-host dissemination and pathogenicity of viruses remains poorly understood. The diversity of henipaviruses and their wide host range and tissue tropism make them particularly appropriate models with which to characterize the drivers of syncytium formation and the implications for virus fitness and pathogenicity. Based on the henipavirus literature, we summarized current knowledge on the mechanisms driving syncytium formation, mostly acquired from in vitro studies, and on the in vivo distribution of syncytia. While these data suggest that syncytium formation widely occurs across henipaviruses, hosts, and tissues, we identified important data gaps that undermined our understanding of the role of syncytium formation in virus pathogenesis. Based on these observations, we propose solutions of varying complexity to fill these data gaps, from better practices in data archiving and publication for in vivo studies, to experimental approaches in vitro.

Sabin Kumar Ranabhat,1 Nishan Raj Rijal,2 Muskan Dubey,3 Arun Kumar Dubey,4 Neelam Dwivedi,5 Arun Kumar Mohan,6 Ravikant Ravikant,7 Ramesh Lolla4 1Department of Pathology, Xavier University School of Medicine, Oranjestad, Aruba; 2Department of Pathology, Chitwan Medical College Teaching Hospital, Bharatpur, Nepal; 3Xavier University School of Medicine, Oranjestad, Aruba; 4Department of Pharmacology, Xavier University School of Medicine, Oranjestad, Aruba; 5Department of Medicine, OSCE and SP Program, Xavier University School of Medicine, Oranjestad, Aruba; 6Department of Physiology, Xavier University School of Medicine, Oranjestad, Aruba; 7Department of Microbiology, Xavier University School of Medicine, Oranjestad, ArubaCorrespondence: Sabin Kumar Ranabhat, Email sabinmd@xusom.comBackground: Hashimoto thyroiditis is an autoimmune disease which is diagnosed based on well-defined clinical and cytological criteria.Purpose: The objective of this research is to study cytomorphological features in patients of Hashimoto thyroiditis and compare the findings with other studies. Literature on morphology of multinucleated giant cells was found to be lacking, and this study has focused on the number and morphology of these cells in this study.Material and Methods: FNAC was done in patients who met the clinical diagnostic criteria of Hashimoto thyroiditis formulated by “Japan Thyroid Association” and smears were analyzed by light microscopy. Data analysis was done by XLSTAT in Microsoft Excel 2010. The Wilcoxon Signed Rank Test was done to analyze the data on multinucleated giant cells. The null hypothesis was that the median of the population of differences between the paired data of small and large giant cells is zero.Results: A total of 26 patients were included in a period of one year. Contrary to observations in other studies, multinucleated giant cells were found in most participants. The Wilcoxon Signed Rank Test proved that small multinucleated giant cells were significantly more common than large multinucleated giant cells in Hashimoto thyroiditis; P value (two-tailed) being < 0.0001 at significance alpha of 0.05. This study has also revealed that a few patients with Hashimoto thyroiditis can have large and very large multinucleated giant cells in a small number. Data on other cytomorphological features were no different than in other studies.Conclusion: The presence of multinucleated giant cells in 92.3% of patients in this study is far higher than in other studies which can have important diagnostic implications. Few large multinucleated giant cells can be present in a small number in a few patients as in Hashimoto thyroiditis.Keywords: Hashimoto thyroiditis, cytomorphology, giant cells

Idiopathic Granulomatous Mastitis (IGM) is an infrequent, benign breast disease that primarily affects women during their childbearing years and can be mistaken for breast cancer. This study aimed to review the clinical, radiological, and histopathological findings of patients with IGM in addition to management and outcome. Retrospective cross-sectional study of biopsy-confirmed IGM at an academic medical center and a private hospital in Amman, Jordan. Fifty-four patients were included, with a mean age of 37.0 ± 9.04 years, mostly presenting with a breast lump (n = 52, 96.3%) and breast pain (n = 45 patients, 84.9%). Approximately half of the patients (51.9%) were parous, and 50% had breastfed for an average duration of 30.37 ± 22.38 months. Most of the patients had either solitary or multiple abscesses on breast ultrasound. Histopathological analysis (n = 35) showed mostly either moderate inflammation (n = 16, 45.7%) or severe inflammation (n = 14, 40%). Two-thirds of the patients underwent surgical interventions at the time of diagnosis, mostly incision and drainage (n = 16, 29%) or surgical excision (n = 7, 13%), and no mastectomies were performed. The most common medical treatment included a combination of antibiotics, corticosteroids, and methotrexate (n = 21, 38.8%). After follow-up, 31 patients remained in remission, 3 experienced relapses, and 3 had a chronic course. The use of corticosteroids was significantly associated with remission (p = 0.035). The presentation and demographics of IGM patients in Jordan were consistent with the existing literature. Prospective research is needed to explore different treatment options and disease outcomes. [ABSTRACT FROM AUTHOR]

Plant-parasitic nematodes cause a serious threat to agronomic food production, and resistance genes against nematodes are scarce in crop plants. As the JA pathway plays an important role in plant defense against RKNs ([15]), this potentially explains the lack of induction of immunity marker genes in galls formed upon nematode infection in tomato I arf8 i mutants ([16]). Keywords: Giant cells; loss of susceptibility; parasitism; post-transcriptional gene silencing; syncytia EN Giant cells loss of susceptibility parasitism post-transcriptional gene silencing syncytia 5422 5425 4 10/04/23 20230929 NES 230929 Plant-parasitic nematodes are among the major biotic factors limiting crop production. Arabidopsis miR827 mediates post-transcriptional gene silencing of its ubiquitin E3 ligase target gene in the syncytium of the cyst nematode Heterodera schachtii to enhance susceptibility. [Extracted from the article]

Root-knot nematodes (RKN) from the genus Meloidogyne induce the dedifferentiation of root vascular cells into giant multinucleate feeding cells. These feeding cells result from an extensive reprogramming of gene expression, and auxin is known to be a key player in their development. However, little is known about how the auxin signal is transmitted during giant cell development. Integrative analyses combining transcriptome and small non-coding RNA datasets with the specific sequencing of cleaved transcripts identified genes targeted by miRNAs in tomato (Solanum lycopersicum) galls. The two auxin-responsive transcription factors ARF8A and ARF8B, and their miRNA167 regulators, were identified as robust gene–miRNA pair candidates to be involved in the tomato response to M. incognita. Spatiotemporal expression analysis using promoter–β-glucuronidase (GUS) fusions showed the up-regulation of ARF8A and ARF8B in RKN-induced feeding cells and surrounding cells. The generation and phenotyping of CRISPR (clustered regularly interspaced palindromic repeats) mutants demonstrated the role of ARF8A and ARF8B in giant cell development and allowed the characterization of their downstream regulated genes. [ABSTRACT FROM AUTHOR]

• Xanthogranulomatous conditions may present as lipid-rich periorbital lesions. • Xanthogranuloma is characterized by lipid-laden Touton giant cells. • Systemic disease can be life-threatening; multidisciplinary work-up is warranted. This report describes an unusual and diagnostically challenging case of subcutaneous soft tissue xanthogranulomas of bilateral orbits of a 58-year-old female patient seen in a private oculoplastics practice. Accurate and timely diagnosis is crucial in xanthogranulomatous diseases so that any systemic manifestations can be identified and addressed in a multidisciplinary fashion. Periorbital xanthogranuloma is a frequent early manifestation of adult xanthogranulomatous disease, and its association with life-threatening systemic disease requires accurate diagnosis and prompt work-up. This case describes an otherwise asymptomatic patient who presented with bilateral orbital masses causing visually significant ptosis, initially diagnosed as soft tissue xanthomas, and later identified as xanthogranulomas. It is important for physicians of all fields, from primary care to surgical subspecialty, to be aware that xanthogranulomatous disease may first present as periorbital lesions and/or orbital masses, and that further work-up for vision and life-threatening systemic disease is warranted. [ABSTRACT FROM AUTHOR]

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is initiated by binding of the viral Spike protein to host receptor angiotensin-converting enzyme 2 (ACE2), followed by fusion of viral and host membranes. Although antibodies that block this interaction are in emergency use as early coronavirus disease 2019 (COVID-19) therapies, the precise determinants of neutralization potency remain unknown. We discovered a series of antibodies that potently block ACE2 binding but exhibit divergent neutralization efficacy against the live virus. Strikingly, these neutralizing antibodies can inhibit or enhance Spike-mediated membrane fusion and formation of syncytia, which are associated with chronic tissue damage in individuals with COVID-19. As revealed by cryoelectron microscopy, multiple structures of Spike-antibody complexes have distinct binding modes that not only block ACE2 binding but also alter the Spike protein conformational cycle triggered by ACE2 binding. We show that stabilization of different Spike conformations leads to modulation of Spike-mediated membrane fusion with profound implications for COVID-19 pathology and immunity.

Only a handful of cell types, including fibroblasts, epithelial, and endothelial cells, can support human cytomegalovirus (CMV) replication in vitro, in striking contrast to the situation in vivo. While the susceptibility of epithelial and endothelial cells to CMV infection is strongly modulated by their anatomical site of origin, multiple CMV strains have been successfully isolated and propagated on fibroblasts derived from different organs. As oral mucosal cells are likely involved in CMV acquisition, we sought to evaluate the ability of infant labial fibroblasts to support CMV replication, compared to that of commonly used foreskin and fetal lung fibroblasts. No differences were found in the proportion of cells initiating infection, or in the amounts of viral progeny produced after exposure to the fibroblast-adapted CMV strain AD169 or to the endothelial cell-adapted strain TB40/E. Syncytia formation was, however, significantly enhanced in infected labial and lung fibroblasts compared to foreskin-derived cells, and did not occur after infection with AD169. Together, these data indicate that fibroblast populations derived from different tissues are uniformly permissive to CMV infection but retain phenotypic differences of potential importance for infection-induced cell-cell fusion, and ensuing viral spread and pathogenesis in different organs.

Primary carcinomas of the lung are vastly represented by the conventional types of adenocarcinomas or squamous cell carcinomas. However, there are other types of non-small cell carcinomas that although uncommon represent a meaningful group that often pose a problem not only in diagnosis but also in classification. Spindle cell and/or giant cell carcinomas, although uncommon represent an important group of primary lung carcinomas. Important to highlight is that current criteria are rather ambiguous and likely not up to date, which renders the classification of these tumors somewhat more obscure. In addition, with the daily use of immunohistochemical stains, the classification of these tumors may also pose a different problem in the proper allocation of these tumors. Proper classification is highly important in the selection process that takes place using such material for molecular analysis. The current molecular characteristics of these tumors are limited and lack more in-depth studies and analyses that can provide specific targets for the treatment of patients with these tumors. The current review attempts to highlight the shortcomings in the current classification and definitions of these neoplasms as well as the more current view regarding these tumors when the use of immunohistochemical stains is employed. [ABSTRACT FROM AUTHOR]

Background and Objectives: Chronic lymphocytic thyroiditis is autoimmune thyroiditis; it is considered as second most common thyroid disorder diagnosed on FNAC following colloid goitre. FNAC is a reliable and efficient method for diagnosing these thyroid lesions. Chronic Lymphocytic thyroiditis frequently affects women, primarily compared to men and is commonly found with hypothyroidism, euthyroidism or every so often with hyperthyroidism. The incidence rate of Hashimoto's thyroiditis is 1-4%, with an occurrence of 30-60/100000 population per year. Autoimmune thyroiditis can be categorized on the cytomorphological features of FNAC. Methods: To compare FNAC cytological findings with TFT in Chronic lymphocytic thyroiditis. One hundred ten patients with thyroid swellings were presented for FNAC examination, serology of TFT and Anti TPO antibodies and Ultrasonography during 2020-2021. In addition, fine needle aspiration cytology was performed using non-aspiration or aspiration techniques. TFT and Anti-TPO antibodies were performed on Avion CLX 120 auto analyser based on the Chemiluminescence method. Result: Out of 110 cases of midline neck swelling presented in our department, Autoimmune Thyroiditis was observed in 43 cases. The most affected age group of lymphocytic thyroiditis was 21-30 years, with the male: female ratio being 1:3. Most of the patients presented with diffuse swelling and few presented with nodular swelling. The Grading of the lymphocytic thyroiditis was done by the criteria used by Bhatia et al Anti-TPO antibody was elevated in 19 cases (26.2%), and TSH was elevated in 28 cases (40.81%). These cases were diagnosed as autoimmune thyroiditis on cytology, clinically and also correlating with radiological findings. Grade 3 lymphoid infiltrate was seen in 53.33% (16/30) cases, and Grade 2, lymphoid infiltrate was seen in eight cases (62.50%). Grade 1 lymphoid infiltrate was seen in five cases (11.63%). Among 43 cases, 28 cases (65.12%) show hypothyroidism, 7 cases (16.28%) show hyper, and 8 cases (18.60%) show Euthyroidism. Among these 43 cases, 26 cases showed diffuse thyroid swelling on ultrasonography, and 7 cases showed solitary nodule. Conclusion: Grade 3 lymphocytic infiltration statistically correlates with anti-TPO and TSH in conjunction with ultrasonography findings of diffuse enlargement of the thyroid gland. The presence of Hurthle cell change, giant cells, anisonucleosus, and granulomas do not find to be any statistical correlation with lymphocytic thyroiditis as these cases are primarily corresponding to Grade 1 and Grade 2. Through this study, we conclude that FNAC remains the gold standard method despite having different diagnostic modalities accessible for diagnosing thyroid lesions. Grading of FNAC Smears depends on lymphocytic infiltration of the thyroid follicles, along with positivity for antithyroid antibodies (anti-TPO antibody) and TSH. These findings are firmly associated with Chronic Lymphocytic Thyroiditis. [ABSTRACT FROM AUTHOR]

Simple Summary: Recently, cells of large size called PGCC (Polyploid Giant Cancer Cells) have emerged as a pillar in cancer development and progression, possibly being the "first cells" from which the cancer starts. PGCC have been studied in cancer tissues from patients and in laboratory models. They have also been found in the blood, occasionally. By applying a method able to detect rare cells in urine, we found these PGCC in the urine of patients with prostate cancer. No study has ever published this finding. Our work is preliminary but deserves to be shared with the scientific community as it opens the way for more studies targeting the role of these PGCC and their possible use as an early and non-invasive marker of prostate cancer development. Prostate cancer is the third cause of cancer-related deaths in men. Its early and reliable diagnosis is still a public health issue, generating many useless prostate biopsies. Prostate cancer cells detected in urine could be the target of a powerful test but they are considered too rare. By using an approach targeting rare cells, we have analyzed urine from 45 patients with prostate cancer and 43 healthy subjects under 50 y.o. We observed a relevant number of giant cells in patients with cancer. Giant cells, named Polyploid Giant Cancer Cells (PGCC), are thought to be involved in tumorigenesis and treatment resistance. We thus performed immune-morphological studies with cancer-related markers such as α-methylacyl-CoA racemase (AMACR), prostate-specific membrane antigen (PSMA), and telomerase reverse transcriptase (TERT) to understand if the giant cells we found are PGCC or other urinary cells. We found PGCC in the urine of 22 patients, including those with early-stage prostate cancer, and one healthy subject. Although these results are preliminary, they provide, for the first time, clinical evidence that prostate cancers release PGCC into the urine. They are expected to stimulate further studies aimed at understanding the role of urinary PGCC and their possible use as a diagnostic tool and therapeutic target. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndromes (MDS) are incurable diseases characterized by dysplastic hematopoietic cells, cytopenias in the blood and an inherent tendency for transformation to secondary acute myeloid leukemia (AML). Since most therapies fail to prevent rapid clonal evolution and disease resistance, new and non-invasive predictive markers are needed to monitor patients and adapt the therapeutic strategy. By using ISET, a very sensitive approach to isolate cells larger than mature leukocytes from peripheral blood samples, we looked for cellular markers in 99 patients (158 samples) with MDS and 66 healthy individuals (76 samples) used as controls. We found a total of 680 Giant Cells, defined as cells having a size of 40 microns or larger in 46 MDS patients (80 samples) and 28 Giant Cells in 11 healthy individuals (11 samples). In order to understand if we had enriched from peripheral blood atypical cells of the megakaryocyte line, we studied the Giant Cells using immunolabeling with megakaryocytes and tumor-specific markers. We report that the Giant Cells we found in the peripheral blood of MDS patients primarily express tumor markers. Our results show that Polyploid Giant Cancer Cells (PGCC), similar to those described in solid tumors, are found in the peripheral blood of patients with MDS and suggest the working hypothesis that they could play a role in hematological malignancies. [ABSTRACT FROM AUTHOR]

Langhans multinucleated giant cells (LGCs) are a specific type of multinucleated giant cell containing a characteristic horseshoe-shaped ring of nuclei that are present within granulomas of infectious etiology. Although cytokines that trigger macrophage activation (such as IFN-γ) induce LGC formation, it is not clear whether cytokines that trigger macrophage differentiation contribute to LGC formation. Here, we found that IL-15, a cytokine that induces M1 macrophage differentiation, programs human peripheral blood adherent cells to form LGCs. Analysis of the IL-15‒treated adherent cell transcriptome identified gene networks for T cells, DNA damage and replication, and IFN-inducible genes that correlated with IL-15 treatment and LGC-type multinucleated giant cell formation. Gene networks enriched for myeloid cells were anticorrelated with IL-15 treatment and LGC formation. Functional studies revealed that T cells were required for IL-15‒induced LGC formation, involving a direct contact with myeloid cells through CD40L-CD40 interaction and IFN-γ release. These data indicate that IL-15 induces LGC formation through the direct interaction of activated T cells and myeloid cells.

Giant cell myocarditis is a rare but often devastating diagnosis. Advances in cardiac imaging and mechanical circulatory support have led to earlier and more frequent diagnoses and successful management. This disease state has wide variation in acuity of presentation, and consequently, optimal treatment ranging from intensity and type of immunosuppression to mechanical circulatory support is not well defined. The following case describes the management of a patient with an unusual presentation of giant cell myocarditis over a 10 year course of advanced heart failure therapies and immunomodulatory support. This case highlights emerging concepts in the management of giant cell myocarditis including sub-acute presentations, challenges in diagnosis, and treatment modalities in the modern era.

Filamentous fungi typically grow as interconnected multinucleate syncytia that can be microscopic to many hectares in size. Mechanistic details and rules that govern the formation and function of these multinucleate syncytia are largely unexplored, including details on syncytial morphology and the regulatory controls of cellular and molecular processes. Recent discoveries have revealed various adaptations that enable fungal syncytia to accomplish coordinated behaviors, including cell growth, nuclear division, secretion, communication, and adaptation of the hyphal network for mixing nuclear and cytoplasmic organelles. In this review, we highlight recent studies using advanced technologies to define rules that govern organizing principles of hyphal and colony differentiation, including various aspects of nuclear and mitochondrial cooperation versus competition. We place these findings into context with previous foundational literature and present still unanswered questions on mechanistic aspects, function, and morphological diversity of fungal syncytia across the fungal kingdom.

BACKGROUND: Sarcomatoid lung carcinoma is a poorly differentiated malignant tumor, which is reported only in the form of clinical cases. Even though hematological alterations are frequent in patients with cancer, only a couple of cases of hyperleukocytosis have been described in this type of cancer, associated with greater aggressiveness and poor prognosis. CLINICAL CASE: A 58-year-old male patient with a history of environmental exposure to organic and inorganic dusts, as well as a high-risk smoking index, with persistent cough, associated with wasting syndrome; the chest tomography showed an image suggestive of a mediastinal tumor, and the laboratory findings showed hyperleukocytosis, suspecting hematological neoplasia; the histopathological study confirmed a tumor of pulmonary origin. CONCLUSIONS: The presentation of an unusual paraneoplastic syndrome in the evolution of a very rare histological lineage lung tumor leads to confusion in the approach and a delay in the diagnosis and definitive treatment. [ABSTRACT FROM AUTHOR]

Introduction: The distinction between giant cell tumors and giant cell granulomas is challenging, as both entities have overlapping diagnostic criteria, especially in oral locations. The two entities have similar clinical and radiological presentations, but they differ in their prognoses. Objective: The main objective of this study was to list the clinical, radiological, histological, and prognostic features of maxillomandibular giant cell tumors and giant cell granulomas cases n order to assess their value as a diagnostic referral factor that may allow the distinction between maxillo-mandibular giant cell granuloma and giant cell tumor. Study design: Data of maxillomandibular giant cell granulomas and giant cell tumors were assessed through a scoping review and a pre-existing systematic review of literature. We have also realized a bicentric retrospective study. Results: Various criteria facilitate the differential diagnosis like age, size, locularity and presence of necrosis zone but not the gender. The most discriminating factors was symptomatology (reported in 72% of GCTs while only 15% of GCGs) and the distribution pattern of giant cells in the stroma (homogeneously dispersed in 80% of GCTs versus grouped in clusters in 86.7% of GCGs). Recurrences were most described for giant cell tumors than giant cell granulomas. Malignant transformation and pulmonary metastasis were exclusively reported for giant cell tumors. Conclusion: As clinical and radiological elements are not sufficient to distinguish between these two entities, immunohistochemistry and molecular genetics can be represent diagnostic biomarkers to distinguish giant cell granulomas and giant cell tumors in oral cavity. We have attempted to define the main criteria for the differentiation of giant cell tumor and giant cell granuloma and propose a decision tree for the management of single maxillomandibular giant cell lesions.

Cysts (CNs) and root-knot nematodes (RKNs) induce specialized feeding cells, syncytia, and giant cells (GCs), respectively, within plant roots. The plant tissues around the GCs usually by respond forming a root swelling called a gall that contains the GCs. The ontogenesis of feeding cells is different. GC formation is a process of new organogenesis from vascular cells, which are still not well characterized, that differentiate into GCs. In contrast, syncytia formation involves the fusion of adjacent cells that have already differentiated. Nonetheless, both feeding sites show an auxin maximum pertinent to feeding site formation. However, data on the molecular divergences and similarities between the formation of both feeding sites regarding auxin-responsive genes are still scarce. We studied genes from the auxin transduction pathways that are crucial during gall and lateral root (LR) development in the CN interaction by using promoterreporter (GUS/LUC)transgenic lines, as well as loss of function lines of Arabidopsis. The promoters pGATA23 and several deletions of pmiR390a were active in syncytia, as were in galls, but pAHP6 or putative up-stream regulators as ARF5/7/19 were not active in syncytia. Additionally, none of these genes seemed to play a key role during cyst nematode establishment in Arabidopsis, as the infection rates in loss of function lines did not show significant differences compared to control Col-0 plants. Furthermore, the presence of only canonical AuxRe elements in their proximal promoter regions is highly correlated with their activation in galls/ GCs (AHP6, LBD16), but those promoters active in syncytia (miR390, GATA23) carry AuxRe overlapping core cis-elements for other transcription factor families (i.e., bHLH, bZIP). Strikingly, in silico transcriptomic analysis showed very few genes upregulated by auxins common to those induced in GCs and syncytia, despite the high number of upregulated IAA responsive genes in syncytia and galls. The complex regulation of auxin transduction pathways, where different members of the auxin response factor (ARF) family may interact with other factors, and the differences in auxin sensitivity, as indicated by the lower induction of the DR5 sensor in syncytia than galls, among other factors, may explain the divergent regulation of auxin responsive genes in the two types of nematode feeding sites. [ABSTRACT FROM AUTHOR]

The root-knot nematode Meloidogyne incognita is a pathogenic pest that causes severe economic loss to agricultural production by forming a parasitic relationship with its hosts. During the development of M. incognita in the host plant roots, giant cells are formed as a nutrient sink. However, the roles of sugar transporters during the giant cells gain sugar from the plant cells are needed to improve. Meanwhile, the eventual function of sugars will eventually be exported transporters (SWEETs) in nematode-plant interactions remains unclear. In this study, the expression patterns of Arabidopsis thaliana SWEETs were examined by inoculation with M. incognita at 3 days post inoculation (dpi) (penetration stage) and 18 dpi (developing stage). We found that few AtSWEETs responded sensitively to M. incognita inoculation, with the highest induction of AtSWEET1 (AT1G21460), a glucose transporter gene. Histological analyses indicated that the b-glucuronidase (GUS) and green fluorescent protein (GFP) signals were observed specifically in the galls of AtSWEET1-GUS and AtSWEET1-GFP transgenic plant roots, suggesting that AtSWEET1 was induced specifically in the galls. Genetic studies have shown that parasitism of M. incognita was significantly affected in atsweet1 compared to wildtype and complementation plants. In addition, parasitism of M. incognita was significantly affected in atsweet10 but not in atsweet13 and atsweet14, expression of which was induced by inoculation with M. incognita. Taken together, these data prove that SWEETs play important roles in plant and nematode interactions. [ABSTRACT FROM AUTHOR]

Root-knot nematodes (RKNs, Meloidogyne spp.) are obligate plant parasites that constitute a significant pest for agriculture worldwide. They penetrate the plant roots, reducing the uptake of water and nutrients, causing a significant impact on crop yield. One alternative on focus now for nematode management is biological control. Rhizobacteria within the Bacillus genus show multiple modes of action against plant-parasitic nematodes (PPNs) that can act alone or in combination. In this context, we evaluated a dual-strain bacteria combination (B. paralicheniformi FMCH001 and B. subtilis FMCH002) to reduce nematode infection in tomato plants. We evaluated mortality of larvae from Meloidogyne javanica in vitro, as well as eggs hatching after the treatment. Atraction, penetration, establishment, and reproduction assays in vitro or in pots in tomato plants infected with M. javanica and treated/untreated with the dual-strain bacteria combination were also performed. Additionally, morphometric parameters comparing giant cells size from galls of treated and untreated plants by using confocal microscopy were also measured. The results showed that this combination of strains has nematicidal properties in the pre-infection phase by decreasing the egg-hatching, juvenile survival, and attractiveness to the roots. Furthermore, nematode establishment, gall formation, and, remarkably, giant cell development was severely impaired after the bacterial treatment, suggesting interference with morphogenetic mechanisms induced by the nematode during GCs development within the plant. Nematode reproduction in tomato plants was reduced independently of the application mode in soil, before or after bacterial treatment. The dual-strain combination was also effective against other PPNs (i.e. Pratylenchus spp.) and in different crops (soybean). Therefore, combining B. paralicheniformis FMCH001 and B. subtilis FMCH002 is an efficient agent for the biological control of Meloidogyne spp. by interfering with different stages of the nematode cycle as a result of multiple modes of action. [ABSTRACT FROM AUTHOR]

Summary: Root‐knot nematodes (RKNs) induce giant cells (GCs) within galls which are characterized by large‐scale gene repression at early stages. However, the epigenetic mechanism(s) underlying gene silencing is (are) still poorly characterized.DNA methylation in Arabidopsis galls induced by Meloidogyne javanica was studied at crucial infection stages (3 d post‐infection (dpi) and 14 dpi) using enzymatic, cytological, and sequencing approaches. DNA methyltransferase mutants (met1, cmt2, cmt3, cmt2/3, drm1/2, ddc) and a DNA demethylase mutant (ros1), were analyzed for RKN resistance/tolerance, and galls were characterized by confocal microscopy and RNA‐seq.Early galls were hypermethylated, and the GCs were found to be the major contributors to this hypermethylation, consistent with the very high degree of gene repression they exhibit. By contrast, medium/late galls showed no global increase in DNA methylation compared to uninfected roots, but exhibited large‐scale redistribution of differentially methylated regions (DMRs). In line with these findings, it was also shown that DNA methylation and demethylation mutants showed impaired nematode reproduction and gall/GC‐development. Moreover, siRNAs that were exclusively present in early galls accumulated at hypermethylated DMRs, overlapping mostly with retrotransposons in the CHG/CG contexts that might be involved in their repression, contributing to their stability/genome integrity. Promoter/gene methylation correlated with differentially expressed genes encoding proteins with basic cell functions. Both mechanisms are consistent with reprogramming host tissues for gall/GC formation.In conclusion, RNA‐directed DNA methylation (RdDM; DRM2/1) pathways, maintenance methyltransferases (MET1/CMT3) and demethylation (ROS1) appear to be prominent mechanisms driving a dynamic regulation of the epigenetic landscape during RKN infection. [ABSTRACT FROM AUTHOR]

We present two cases of very uncommon, undifferentiated pancreatic carcinoma (UPC) with osteoclastic cells. First case is a 52-year-old female with no previous health issues presented with unintentional, significant weight loss, not specified epigastric pain and microcytic anemia. After clinical examination the pancreatic neoplasm was found. Histopathological analysis suggested UPC. Four years later, MSCT scan discovered solid mass in lung and after histopathological analysis metastasis of UPC. Second case is a 72-year-old male with past medical history of diabetes type 2 and hypothyreosis who presented with an epigastric pain. Clinical diagnosis was pancreatic neoplasm. After histopathological examination undifferentiated pancreatic carcinoma with osteoclastic giant cells was diagnosed.

Cysts (CNs) and root-knot nematodes (RKNs) induce specialized feeding cells, syncytia, and giant cells (GCs), respectively, within plant roots. The plant tissues around the GCs usually by respond forming a root swelling called a gall that contains the GCs. The ontogenesis of feeding cells is different. GC formation is a process of new organogenesis from vascular cells, which are still not well characterized, that differentiate into GCs. In contrast, syncytia formation involves the fusion of adjacent cells that have already differentiated. Nonetheless, both feeding sites show an auxin maximum pertinent to feeding site formation. However, data on the molecular divergences and similarities between the formation of both feeding sites regarding auxin-responsive genes are still scarce. We studied genes from the auxin transduction pathways that are crucial during gall and lateral root (LR) development in the CN interaction by using promoter-reporter (GUS/LUC)transgenic lines, as well as loss of function lines of Arabidopsis. The promoters pGATA23 and several deletions of pmiR390a were active in syncytia, as were in galls, but pAHP6 or putative up-stream regulators as ARF5/7/19 were not active in syncytia. Additionally, none of these genes seemed to play a key role during cyst nematode establishment in Arabidopsis, as the infection rates in loss of function lines did not show significant differences compared to control Col-0 plants. Furthermore, the presence of only canonical AuxRe elements in their proximal promoter regions is highly correlated with their activation in galls/GCs (AHP6, LBD16), but those promoters active in syncytia (miR390, GATA23) carry AuxRe overlapping core cis-elements for other transcription factor families (i.e., bHLH, bZIP). Strikingly, in silico transcriptomic analysis showed very few genes upregulated by auxins common to those induced in GCs and syncytia, despite the high number of upregulated IAA responsive genes in syncytia and galls. The complex regulation of auxin transduction pathways, where different members of the auxin response factor (ARF) family may interact with other factors, and the differences in auxin sensitivity, as indicated by the lower induction of the DR5 sensor in syncytia than galls, among other factors, may explain the divergent regulation of auxin responsive genes in the two types of nematode feeding sites.

Root-knot nematodes (RKNs, Meloidogyne spp.) are obligate plant parasites that constitute a significant pest for agriculture worldwide. They penetrate the plant roots, reducing the uptake of water and nutrients, causing a significant impact on crop yield. One alternative on focus now for nematode management is biological control. Rhizobacteria within the Bacillus genus show multiple modes of action against plant-parasitic nematodes (PPNs) that can act alone or in combination. In this context, we evaluated a dual-strain bacteria combination (B. paralicheniformi FMCH001 and B. subtilis FMCH002) to reduce nematode infection in tomato plants. We evaluated mortality of larvae from Meloidogyne javanica in vitro, as well as eggs hatching after the treatment. Atraction, penetration, establishment, and reproduction assays in vitro or in pots in tomato plants infected with M. javanica and treated/ untreated with the dual-strain bacteria combination were also performed. Additionally, morphometric parameters comparing giant cells size from galls of treated and untreated plants by using confocal microscopy were also measured. The results showed that this combination of strains has nematicidal properties in the pre-infection phase by decreasing the egg-hatching, juvenile survival, and attractiveness to the roots. Furthermore, nematode establishment, gall formation, and, remarkably, giant cell development was severely impaired after the bacterial treatment, suggesting interference with morphogenetic mechanisms induced by the nematode during GCs development within the plant. Nematode reproduction in tomato plants was reduced independently of the application mode in soil, before or after bacterial treatment. The dual-strain combination was also effective against other PPNs (i.e. Pratylenchus spp.) and in different crops (soybean). Therefore, combining B. paralicheniformis FMCH001 and B. subtilis FMCH002 is an efficient agent for the biological control of Meloidogyne spp. by interfering with different stages of the nematode cycle as a result of multiple modes of action.

Immunoglobulin light chain amyloidosis can be either systemic or localized. Although these conditions share a similar name, they are strikingly different. Localized light chain amyloidosis has been challenging to characterize due to its lower incidence and highly heterogeneous clinical presentation. Here, we review the emerging literature, emphasizing recent reports on large cohorts of patients with localized amyloidosis, and provide insights into this condition's pathology and natural history. We find that patients with localized amyloidosis have an excellent prognosis with overall survival similar to that of the general population. Furthermore, the risk of progression to systemic disease is low and likely represents initial mischaracterization as localized disease. Therefore, we argue for the incorporation of more sensitive techniques to rule out systemic disease at diagnosis. Despite increasing mechanistic understanding of this condition, much remains to be discovered regarding the cellular clonal evolution and the molecular processes that give rise to localized amyloid formation. While localized surgical resection of symptomatic disease is typically the treatment of choice, the presentation of this disease across the spectrum of plasmacytic B-cell lymphoproliferative disorders, and the frequent lack of an identifiable neoplastic clone, can make therapy selection a challenge in the uncommon situation that systemic chemotherapy is required. [ABSTRACT FROM AUTHOR]

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Congenital bile acid synthesis defect type 3 is a rare metabolic liver disease with only eight patients reported in literature. We describe clinical, pathological and molecular features for a ninth patient. A 4-month-old infant presented to us with conjugated hyperbilirubinemia. His liver biopsy revealed giant cell change, steatosis, and activity with diffuse fibrosis. Immunostaining with bile salt export pump showed preserved canalicular pattern and γ-glutamyl transferase 1 staining showed unusual complete membranous pattern. Genetic workup revealed homozygous single base pair duplication in exon 3 of the CYP7B1 gene. He succumbed to liver disease at 7 months of age. [ABSTRACT FROM AUTHOR]

Cyst nematodes establish permanent feeding structures called syncytia inside the host root vasculature, disrupting the flow of water and minerals. In response, plants form WOX11-mediated adventitious lateral roots at nematode infection sites. WOX11 adventitious lateral rooting modulates tolerance to nematode infections; however, whether this also benefits nematode parasitism remains unknown. Here, we report on bioassays using a 35S::WOX11-SRDX transcriptional repressor mutant to investigate whether WOX11 adventitious lateral rooting promotes syncytium development and thereby female growth and fecundity. Moreover, we chemically inhibited cellulose biosynthesis to verify if WOX11 directly modulates cell wall plasticity in syncytia. Finally, we performed histochemical analyses to test if WOX11 mediates syncytial cell wall plasticity via reactive oxygen species (ROS). Repression of WOX11-mediated transcription specifically enhanced the radial expansion of syncytial elements, increasing both syncytium size and female offspring. The enhanced syncytial hypertrophy observed in the 35S::WOX11-SRDX mutant could be phenocopied by chemical inhibition of cellulose biosynthesis and was associated with elevated levels of ROS at nematode infection sites. We, therefore, conclude that WOX11 restricts radial expansion of nematode-feeding structures and female growth and fecundity, likely by modulating ROS-mediated cell wall plasticity mechanisms. Remarkably, this novel role of WOX11 in plant cell size control is distinct from WOX11 adventitious lateral rooting underlying disease tolerance., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Immunoglobulin light chain amyloidosis can be either systemic or localized. Although these conditions share a similar name, they are strikingly different. Localized light chain amyloidosis has been challenging to characterize due to its lower incidence and highly heterogeneous clinical presentation. Here, we review the emerging literature, emphasizing recent reports on large cohorts of patients with localized amyloidosis, and provide insights into this condition’s pathology and natural history. We find that patients with localized amyloidosis have an excellent prognosis with overall survival similar to that of the general population. Furthermore, the risk of progression to systemic disease is low and likely represents initial mischaracterization as localized disease. Therefore, we argue for the incorporation of more sensitive techniques to rule out systemic disease at diagnosis. Despite increasing mechanistic understanding of this condition, much remains to be discovered regarding the cellular clonal evolution and the molecular processes that give rise to localized amyloid formation. While localized surgical resection of symptomatic disease is typically the treatment of choice, the presentation of this disease across the spectrum of plasmacytic B-cell lymphoproliferative disorders, and the frequent lack of an identifiable neoplastic clone, can make therapy selection a challenge in the uncommon situation that systemic chemotherapy is required.