A protease and a lipoprotein jointly modulate the conserved ExoR-ExoS-ChvI signaling pathway critical in Sinorhizobium meliloti for symbiosis with legume hosts.

Sinorhizobium meliloti is a model alpha-proteobacterium for investigating microbe-host interactions, in particular nitrogen-fixing rhizobium-legume symbioses. Successful infection requires complex coordination between compatible host and endosymbiont, including bacterial production of succinoglycan, also known as exopolysaccharide-I (EPS-I). In S. meliloti EPS-I production is controlled by the conserved ExoS-ChvI two-component system. Periplasmic ExoR associates with the ExoS histidine kinase and negatively regulates ChvI-dependent expression of exo genes, necessary for EPS-I synthesis. We show that two extracytoplasmic proteins, LppA (a lipoprotein) and JspA (a lipoprotein and a metalloprotease), jointly influence EPS-I synthesis by modulating the ExoR-ExoS-ChvI pathway and expression of genes in the ChvI regulon. Deletions of jspA and lppA led to lower EPS-I production and competitive disadvantage during host colonization, for both S. meliloti with Medicago sativa and S. medicae with M. truncatula. Overexpression of jspA reduced steady-state levels of ExoR, suggesting that the JspA protease participates in ExoR degradation. This reduction in ExoR levels is dependent on LppA and can be replicated with ExoR, JspA, and LppA expressed exogenously in Caulobacter crescentus and Escherichia coli. Akin to signaling pathways that sense extracytoplasmic stress in other bacteria, JspA and LppA may monitor periplasmic conditions during interaction with the plant host to adjust accordingly expression of genes that contribute to efficient symbiosis. The molecular mechanisms underlying host colonization in our model system may have parallels in related alpha-proteobacteria.

Comparative Incidences and Biological Outcomes for Thymoma in Various Rat Strains in National Toxicology Program Studies.

Thymomas from 277 Fischer 344/N (F344/N), 10 Sprague Dawley (HSD:Sprague Dawley SD) (SD), 129 Wistar Han [Crl:WI(Han)] (WH), and 4 Wistar Outbred (WO) rats were reviewed from long-term studies in the National Toxicology Program (NTP) database. The incidence of thymomas in F344/N rats was slightly higher in males than in females, while the incidences in SD and WH rats were higher in females than in males. Only male WO rats were used in NTP studies. Of the 277 thymomas in F344/N rats, 235 (84.8%) were benign and 42 (15.2%) malignant, 14 of which exhibited metastasis. Of the 10 thymomas in SD rats, 5 (50%) were benign and 5 (50%) were malignant, one of which exhibited metastasis. Of the 129 thymomas in WH rats, 126 (98%) were benign and 3 (2%) were malignant, 1 with metastasis. Of the 4 thymomas in WO rats, 3 (75%) were benign and 1 (25%) was malignant, with no metastases. Malignant thymomas in F344/N and WH rats showed a propensity to be the cause of death and to result in early mortality, whereas the benign thymomas were associated less often with decreased survival. No occurrences of this neoplasm were reported to be related to exposure to any test articles.

Proceedings of the 2010 National Toxicology Program Satellite Symposium.

The 2010 annual National Toxicology Program (NTP) Satellite Symposium, entitled "Pathology Potpourri," was held in Chicago, Illinois, in advance of the scientific symposium sponsored jointly by the Society of Toxicologic Pathology (STP) and the International Federation of Societies of Toxicologic Pathologists (IFSTP). The goal of the annual NTP Symposium is to present current diagnostic pathology or nomenclature issues to the toxicologic pathology community. This article presents summaries of the speakers' presentations, including diagnostic or nomenclature issues that were presented, along with select images that were used for voting or discussion. Some topics covered during the symposium included a comparison of rat and mouse hepatocholangiocarcinoma, a comparison of cholangiofibrosis and cholangiocarcinoma in rats, a mixed pancreatic neoplasm with acinar and islet cell components, an unusual preputial gland tumor, renal hyaline glomerulopathy in rats and mice, eosinophilic substance in the nasal septum of mice, INHAND nomenclature for proliferative and nonproliferative lesions of the CNS/PNS, retinal gliosis in a rat, fibroadnexal hamartoma in rats, intramural plaque in a mouse, a treatment-related chloracne-like lesion in mice, and an overview of mouse ovarian tumors.

Proceedings of the 2009 National Toxicology Program Satellite Symposium.

The National Toxicology Program (NTP) Satellite Symposium is a one-day meeting that is held in conjunction with the annual Society of Toxicologic Pathology (STP) meeting. The topic of the 2009 Symposium was "Tumor Pathology and INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) Nomenclature." The goal of this article is to provide summaries of each speaker's presentation, including the diagnostic or nomenclature issues that were presented, along with a few select images that were used for voting. The results of the voting process and interesting points of discussion that were raised during the presentation are also provided. A supplemental file with voting choices and voting results for each case presented at the symposium is available at http://tpx.sagepub.com/supplemental.

Hypercalcemia associated with gastric pythiosis in a dog.

A 20-month-old castrated male Labrador Retriever with a 3-month history of anorexia, weight loss, and vomiting was evaluated. Plasma biochemical abnormalities included marked hyperglobulinemia and hypercalcemia. Serum levels of parathyroid hormone, parathyroid hormone-related protein, 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D were either low or within reference intervals. Gastric wall thickening and abdominal lymphadenomegaly were observed with abdominal ultrasonography. Cytologic evaluation of a sample obtained via fine-needle aspiration of the gastric wall revealed pyogranulomatous inflammation and numerous poorly stained hyphae. Partial gastrectomy was performed, and a diagnosis of gastric pythiosis was made by immunohistochemical staining of infected gastric tissue, as well as by immunoblot serology. This case demonstrates that diagnostic samples for cytologic evaluation can be obtained by fine-needle aspiration of Pythium insidiosum-infected tissues and that a presumptive diagnosis can be made by examination of a Romanowsky-stained smear. Furthermore, pythiosis should be considered as a differential diagnosis for hypercalcemia, especially in young dogs with inflammatory lesions that have a granulomatous component. The mechanism for the hypercalcemia in this dog was not determined; however, calcium concentrations normalized after surgical resection of the gastric lesion.

Liver aspirate from a Shar Pei dog.

A 5-year-old, neutered male, Shar Pei dog was presented with weight loss, anorexia, lethargy, stranguria, and distal limb edema. Clinicopathologic abnormalities included anemia, an inflammatory leukogram, azotemia, icterus, urinary tract infection, and hepatomegaly with a markedly hypoechoic liver. Cytologic findings in a fine-needle aspirate of the liver included large amounts of amorphous, pink, extracellular matrix between hepatocytes. The amorphous material was congophilic using Congo red stain on a hepatic cytology specimen and green birefringent areas were observed under polarized light, confirming the presence of amyloid. The dog was euthanized and a necropsy was done. Histopathologic evaluation using H&E and Congo red staining confirmed amyloid deposits within the liver, kidneys, intestinal vessels, pancreas, and mesenteric ganglia. Immunohistochemical staining of liver and kidney sections using anti-AA amyloid and anti-P component antibodies confirmed the presence of AA amyloid. In this case, we demonstrated that Congo red staining and polarized light microscopy are a useful diagnostic technique in cytologic specimens of suitable thickness for confirming the presence of amyloid.