A clonogenic bone marrow progenitor specific for macrophages and dendritic cells

Macrophages and dendritic cells (DCs) are crucial for immune and inflammatory responses and belong to a network of cells that has been termed the mononuclear phagocyte system (MPS). However, the origin and lineage of these cells remain poorly understood. Here, we describe the isolation and clonal analysis of a mouse bone marrow progenitor that is specific for monocytes, several macrophage subsets, and resident spleen DCs in vivo. It was also possible to recapitulate this differentiation in vitro by using treatment with the cytokines macrophage colony-stimulating factor and granulocyte-macrophage colony-stimulating factor. Thus, macrophages and DCs appear to renew from a common progenitor, providing a cellular and molecular basis for the concept of the MPS.     

Common Kibra alleles are associated with human memory performance

Human memory is a polygenic trait. We performed a genome-wide screen to identify memory-related gene variants. A genomic locus encoding the brain protein KIBRA was significantly associated with memory performance in three independent, cognitively normal cohorts from Switzerland and the United States. Gene expression studies showed that KIBRA was expressed in memory-related brain structures. Functional magnetic resonance imaging detected KIBRA allele-dependent differences in hippocampal activations during memory retrieval. Evidence from these experiments suggests a role for KIBRA in human memory.     

Cerebrospinal fluid from a 10-year-old dog with a single seizure episode

A cerebrospinal fluid sample collected from the cerebellomedullary cistern of a 10-year-old Shetland Sheepdog with a recent history of seizures was submitted for fluid analysis and cytologic examination. Key findings included a total nucleated cell count of 520/microL (reference interval 0-5 cells/microL), with a predominance of mononuclear cells, a protein concentration of 51.8 mg/dL (reference interval 0-35 mg/dL), and a glucose concentration of 44.7 mg/dL (reference interval 52-105 mg/dL). There was marked atypia of the mononuclear cells, with abundant eosinophilic cytoplasm, marked anisocytosis and anisokaryosis, occasional binucleated cells, mitotic figures, and rare erythrophagia. The cytologic interpretation was marked, monocytoid-rich, mixed cell pleocytosis with cellular atypia worrisome for neoplasia. In addition to histiocytic neoplasia, differentials included granulomatous meningoencephalomyelitis, necrotizing meningoencephalitis, and granulomatous inflammation. The dog did not respond to anti-inflammatory and anticonvulsive therapy. At necropsy, a mass involving the meninges and subtending the neuropil of the right temporal lobe of the cerebrum was found. Histologically, the mass was composed of large, bizarre histiocytic cells with multinucleated forms and numerous mitotic figures. Using immunochemistry on cytologic and histologic samples, the pleomorphic histiocytic cells were positive for CD1c, CD11ad, CD45, lysozyme, and vimentin, and were negative for CD3, CD4, CD79a, CD90, and pancytokeratin. These findings supported a diagnosis of primary CNS malignant histiocytosis of dendritic antigen-presenting cell (CD1c+) origin. To our knowledge, this is only the third reported case of primary CNS histiocytic sarcoma in dogs, and the first to demonstrate strong immunochemical evidence for dendritic antigen-presenting cell origin.     

Erythrophagocytic multiple myeloma in a cat

A 7-year-old neutered male domestic shorthair cat was presented to the Veterinary Medical Teaching Hospital at the University of Georgia for further evaluation of a suspected osteolytic lesion of the left 10th rib. Results of a CBC and biochemistry profile revealed mild nonregenerative anemia, hyperproteinemia, hyperglobulinemia, and hypercalcemia. Serum protein electrophoresis was consistent with a monoclonal gammopathy. Marked proteinuria with an increased urine protein to creatinine ratio was found. Cytologic examination of the liver, spleen, and bone marrow revealed numerous plasma cells, many of which were erythrophagocytic. Within the bone marrow, the plasma cells contained phagocytosed metarubricytes in addition to phagocytosed erythrocytes. A diagnosis of erythrophagocytic multiple myeloma was made and treatment with prednisone and melphalan was begun. Four weeks after presentation, the cat was euthanized due to clinical deterioration. A complete necropsy was performed. The distal one-third of the left 10th rib was completely absent. Histologically, there was no evidence for osteolysis or neoplastic cells in the remaining portion of the rib. However, large sheets of plasma cells were found infiltrating the spleen and bone marrow. Moderate erythrophagocytosis by the plasma cells was observed in both organs. The plasma cells, including the erythrophagocytic cells, were positive for CD79alpha by immunohistochemical staining. Erythrophagocytosis by plasma cells as a cause of anemia is uncommon in people with multiple myeloma and is rare in animals. To our knowledge, this is the first report of erythrophagocytic plasma cells in a cat with multiple myeloma.     

Linking long-term dietary patterns with gut microbial enterotypes

Diet strongly affects human health, partly by modulating gut microbiome composition. We used diet inventories and 16S rDNA sequencing to characterize fecal samples from 98 individuals. Fecal communities clustered into enterotypes distinguished primarily by levels of Bacteroides and Prevotella. Enterotypes were strongly associated with long-term diets, particularly protein and animal fat (Bacteroides) versus carbohydrates (Prevotella). A controlled-feeding study of 10 subjects showed that microbiome composition changed detectably within 24 hours of initiating a high-fat/low-fiber or low-fat/high-fiber diet, but that enterotype identity remained stable during the 10-day study. Thus, alternative enterotype states are associated with long-term diet.     

Heat Shock Protein Regulation in Rainbow Trout,Oncorhynchus mykiss,is Altered by Dietary Soybean Meal Inclusion and Anti‐Phopholipase A2 Antibody

Heat shock proteins (Hsps) can promote integrity of damaged intestinal epithelial tissues. The aim of this study was to determine the effects of a commercially available anti‐phospholipase A₂ antibody on growth, feed efficiency, Hsp expression, and intestinal health of rainbow trout fed diets containing high levels of soybean meal (SBM). Six practical‐type diets (45% protein; 15% fat) were formulated to contain 0, 17.5, or 35% SBM with and without antibody. Each diet was fed to three replicate tanks of fish (20 fish/tank; initial weight 21 g) for 9 wk. RNA was isolated from liver and intestinal tissues (n = 3/tank) to detect alterations in Hsp 27, Hsp 70, and Hsp 90 expression. Fish fed a diet containing 35% SBM had decreased growth and intestinal damage. Hsp 27 and Hsp 90 mRNA was elevated in fish fed 35% SBM. Fish fed 35% SBM with antibody had lower Hsp 90 mRNA expression than fish without antibody. These data indicate that feeding rainbow trout high levels of SBM alters the expression of some Hsps and anti‐phospholipase A₂ antibody supplementation does not normalize growth or prevent distal enteritis in fish fed 35% SBM.     

Immunopathology of vesicular cutaneous lupus erythematosus in the rough collie and Shetland sheepdog: a canine homologue of subacute cutaneous lupus erythematosus in humans

Clinical and histological features of an erosive disease in the rough collie and Shetland sheepdog are most consistent with a vesicular variant of cutaneous lupus erythematosus (VCLE). This paper reports the immunopathological findings of canine VCLE using samples from 17 affected dogs. Lesional skin sections were stained with monoclonal antibodies specific for CD3 (11 dogs) or a panel of monoclonal antibodies specific for leukocyte antigens (two dogs). Apoptotic cells were detected using the TUNEL method in 12 cases. Direct (14 dogs) and indirect immunofluorescence tests (five dogs) were also performed. Circulating antibodies to extractable nuclear antigens (ENA) were surveyed in 11 dogs by immunoblotting and ELISA. The predominant cells at the dermal-epidermal interface were identified as CD3(+) T lymphocytes expressing CD4 or CD8 and CD1(+) dendritic antigen presenting cells. In 7/12 dogs (58%), apoptosis of basal keratinocyte nuclei was present. Up-regulation of MHCII and ICAM-1 was observed on basal keratinocytes from the two dogs examined. Direct immunofluorescence revealed deposition of immunoglobulins bound to the cytoplasm of keratinocytes (6/14 dogs; 43%), to the dermal-epidermal junction (7/14 dogs; 50%), or to superficial dermal venules (13/14 dogs; 93%). Circulating IgG auto-antibodies targeting one or more ENA were detected in nine (82%) and eight (73%) of 11 dogs by immunoblotting and ELISA, respectively. These auto-antibodies recognized Ro/SSA and/or La/SSB in four (36%) and six (55%) of 11 dogs respectively by these two methods. Altogether, results of these studies provide evidence supporting the hypothesis that canine VCLE is an immunological homologue of subacute cutaneous lupus erythematosus in humans.     

Numerical investigation of the influence of texture,surface drip emitter discharge rate and initial soil moisture condition on wetting pattern size

Knowledge of the dimensions of the wetted zone formed under point source surface drip irrigation is essential to the design of cost-effective and efficient irrigation systems. Numerical simulations were carried out with Hydrus-2D/3D to investigate the influence of emitter discharge rates and initial soil moisture conditions on the wetting pattern dimensions of a series of soils with varying textures. Numerical simulations of simple 2D soil tank irrigation experiments were also conducted on two soil types. Based on the simulation results, the parameters of the Schwartzman and Zur model were refined. The results showed a small influence of discharge rates >1 L h^?1 on the size of the wetting pattern. The only major difference was observed for the rates lower than 0.5 L h^?1, where the largest wetting patterns were observed. Higher initial soil water content caused larger wetting pattern sizes in all directions. When compared to the 2D tank experimental results, Hydrus-2D/3D predicted the wetting pattern dimensions with a relatively small root mean square error not exceeding 2.6 cm. The numerical data obtained for a wide range of textures provided the opportunity to refine the parameters of the Schwartzman and Zur model, which, when compared to experimental data from the literature, provided good estimates of wetting pattern dimensions. This suggests that this simple model, for which the only soil parameter required is the saturated hydraulic conductivity, could provide a valuable and practical tool for irrigation design.     

Gas disks to gas giants: simulating the birth of planetary systems

The ensemble of now more than 250 discovered planetary systems displays a wide range of masses, orbits and, in multiple systems, dynamical interactions. These represent the end point of a complex sequence of events, wherein an entire protostellar disk converts itself into a small number of planetary bodies. Here, we present self-consistent numerical simulations of this process, which produce results in agreement with some of the key trends observed in the properties of the exoplanets. Analogs to our own solar system do not appear to be common, originating from disks near the boundary between barren and (giant) planet-forming.