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2.
Nature ; 579(7798): 250-255, 2020 03.
Article in English | MEDLINE | ID: mdl-32161389

ABSTRACT

The lithified lower oceanic crust is one of Earth's last biological frontiers as it is difficult to access. It is challenging for microbiota that live in marine subsurface sediments or igneous basement to obtain sufficient carbon resources and energy to support growth1-3 or to meet basal power requirements4 during periods of resource scarcity. Here we show how limited and unpredictable sources of carbon and energy dictate survival strategies used by low-biomass microbial communities that live 10-750 m below the seafloor at Atlantis Bank, Indian Ocean, where Earth's lower crust is exposed at the seafloor. Assays of enzyme activities, lipid biomarkers, marker genes and microscopy indicate heterogeneously distributed and viable biomass with ultralow cell densities (fewer than 2,000 cells per cm3). Expression of genes involved in unexpected heterotrophic processes includes those with a role in the degradation of polyaromatic hydrocarbons, use of polyhydroxyalkanoates as carbon-storage molecules and recycling of amino acids to produce compounds that can participate in redox reactions and energy production. Our study provides insights into how microorganisms in the plutonic crust are able to survive within fractures or porous substrates by coupling sources of energy to organic and inorganic carbon resources that are probably delivered through the circulation of subseafloor fluids or seawater.


Subject(s)
Aquatic Organisms/genetics , Aquatic Organisms/metabolism , Energy Metabolism/genetics , Geologic Sediments/microbiology , Microbiota/genetics , Oceans and Seas , Carbon Cycle/genetics , Gene Expression Profiling
3.
Pediatr Transplant ; 16(6): E229-34, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22032720

ABSTRACT

Castleman disease is a rare hematologic disorder, closely linked to the HHV-8, and most commonly observed in immunocompromised individuals. Thirteen months following a liver transplant for CPS-1 defect, a 15-month-old boy presented with fevers, anemia, and growth retardation. Abdominal CT scan showed splenomegaly and generalized lymphadenopathy. Histology of chest wall lymph nodes revealed a mixed CD3+ T-cell and CD20+ B-cell population with atretic germinal centers consistent with multicentric Castleman disease. Qualitative DNA PCR detected HHV-8 in the resected lymph node and in the blood, supporting the diagnosis. Immunosuppression was tapered, and he was transitioned from tacrolimus to sirolimus. His graft function remained stable, and repeat imaging showed regression of the lymphadenopathy. The child is living one yr after Castleman disease diagnosis with a well-functioning graft. Castleman disease is a potential complication of solid organ transplant and HHV-8 infection. Reduction in immunosuppression and switch to sirolimus may be an effective strategy to treat this condition.


Subject(s)
Castleman Disease/complications , Liver Failure/complications , Liver Failure/therapy , Liver Transplantation/methods , Adolescent , Adult , Antigens, CD20/biosynthesis , B-Lymphocytes/metabolism , CD3 Complex/biosynthesis , Castleman Disease/diagnosis , Graft Survival , Herpesvirus 8, Human/genetics , Humans , Immunosuppressive Agents/therapeutic use , Infant, Newborn , Liver Transplantation/adverse effects , Lymphatic Diseases/diagnosis , Male , Middle Aged , Polymerase Chain Reaction , Sirolimus/administration & dosage , Splenomegaly/diagnosis , T-Lymphocytes/metabolism , Tacrolimus/administration & dosage , Tomography, X-Ray Computed/methods
4.
Mod Pathol ; 22(5): 627-32, 2009 May.
Article in English | MEDLINE | ID: mdl-19287463

ABSTRACT

Urothelial papillomas and low-grade urothelial carcinomas have shown a high incidence of fibroblast growth factor receptor 3 (FGFR3) mutations and are associated with a favorable prognosis. The association of FGFR3 mutations with inverted papillomas is less known. We analyzed 20 cases of inverted papilloma in the urinary tract. Mutations of FGFR3 (exons 7, 10, and 15) and TP53 genes were evaluated by DNA sequencing in these cases. Point mutations of the FGFR3 gene were identified in 45% (9 of 20) of inverted papillomas with four cases exhibiting mutations at multiple exons. Seven cases had exon 7 mutations containing R248C, S249T, L259L, P260P, and V266M. Two cases had exon 10 and 15 mutations including A366D, H412H, E627D, D641N, and H643D; five cases had N653H. The most frequent mutation was identified at R248C. None of the inverted papillomas exhibited mutations in TP53. During a mean follow-up of 78 months, none had recurrence or developed urothelial carcinoma. These findings support the concept that low-grade and low-stage urothelial neoplasms arise in a background of molecular changes that are distinctly different from the molecular changes of high-grade and high-stage urothelial cancers.


Subject(s)
Papilloma, Inverted/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Tumor Suppressor Protein p53/genetics , Urinary Bladder Neoplasms/genetics , Adult , Aged , DNA Mutational Analysis , Female , Humans , Incidence , Male , Middle Aged , Mutation , Polymerase Chain Reaction
5.
Hum Pathol ; 38(7): 963-977, 2007 Jul.
Article in English | MEDLINE | ID: mdl-17574946

ABSTRACT

Most bladder tumors arise from the urothelium. However, there are several uncommon but significant malignant bladder lesions that must be differentiated from urothelial carcinomas and from benign lesions of the bladder. The second half of this two-part review will describe rare nonurothelial malignant tumors of the urinary bladder including leiomyosarcoma, rhabdomyosarcoma, angiosarcoma, malignant fibrous histiocytoma (undifferentiated sarcoma), primitive neuroectodermal tumor, malignant peripheral nerve sheath tumor, hemangiopericytoma, and alveolar soft-parts sarcoma. Common clinical presentations, morphologic characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. Because the distinction between malignant and benign lesions has significant therapeutic and prognostic implications, key factors for differentiating them are presented.


Subject(s)
Soft Tissue Neoplasms/pathology , Urinary Bladder Neoplasms/pathology , Diagnosis, Differential , Hemangiopericytoma/pathology , Histiocytoma, Malignant Fibrous/pathology , Humans , Immunohistochemistry , Nerve Sheath Neoplasms/pathology , Neuroectodermal Tumors, Primitive/pathology , Sarcoma/pathology
6.
Hum Pathol ; 38(6): 807-23, 2007 Jun.
Article in English | MEDLINE | ID: mdl-17509394

ABSTRACT

Most bladder tumors arise from the urothelium. However, there are several uncommon but significant bladder lesions that must be differentiated from urothelial carcinomas. These include both benign and malignant spindle cell lesions. The first half of this 2-part review will describe benign myofibroblastic proliferations including inflammatory myofibroblastic tumor and postoperative spindle cell nodule; benign neoplasms including leiomyoma, hemangioma, neurofibroma, and schwannoma; and tumors of uncertain malignant potential including paraganglioma, granular cell tumor, and perivascular epithelioid cell tumor. Common clinical presentations, morphological characteristics, and immunohistochemical features are described to aid the practicing pathologist in the identification of these entities. This review also describes current theories as to the pathogenesis of inflammatory myofibroblastic tumor and postoperative spindle cell nodule and details the current molecular markers identifying several of these lesions.


Subject(s)
Soft Tissue Neoplasms/pathology , Urinary Bladder Neoplasms/pathology , Animals , Biomarkers, Tumor/analysis , Diagnosis, Differential , Humans , Immunohistochemistry , Soft Tissue Neoplasms/metabolism , Urinary Bladder Neoplasms/metabolism
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