Larval growth rate is associated with the composition of the gut microbiota in the Glanville fritillary butterfly.

The rapidly increasing body of literature on commensal microbiota has revealed a large phylotypic and functional diversity of microbes associated with vertebrates and invertebrates. In insects, the gut microbiota plays a role in digestion and metabolism of the host as well as protects the host against pathogens. In the study reported here, we sampled gut microbiota of the larvae of the Glanville fritillary butterfly (Melitaea cinxia). The larvae were collected from the field or reared in the laboratory. This butterfly has two host plant species, Plantago lanceolata and Veronica spicata, and the host plant species is known from previous studies to influence larval growth rate. However, our results demonstrate that about 50 % of the variation in larval growth rate can be attributed to the effect of the gut microbial composition plus the joint effect of microbiota and the host plant species, while host plant species alone makes no significant contribution. Our results support previous studies showing that diet influences the gut microbiota but, more unexpectedly, that the composition of the gut microbiota significantly influences larval growth rate. We suggest that host plant effects on larval growth and development observed in many previous studies may be mediated via the gut microbiota. While we measured the growth rate only in laboratory-reared larvae, the similarity of the gut microbial composition between samples from field-collected and laboratory-reared larvae suggests that the results can be generalized to natural conditions.

Identification of ETS-like transcription factor 4 as a novel androgen receptor target in prostate cancer cells.

Transcriptional control by androgens via androgen receptor (AR) is strongly involved in prostate cancer development, but the critical target genes have remained elusive. We have characterized E twenty-six-like transcription factor 4 (ELK4) (also known as serum response factor accessory protein 1) as a novel AR target in human prostate cancer cells. In-silico screening identified three putative AR response elements (AREs) within -10 kb from the transcription start site of ELK4. Both ARE1 at -167/-153 and ARE2 at -481/-467 bound AR in vitro and mediated androgen induction as isolated elements in transcription assays in non-prostate cells. However, merely the ARE2 that cooperates with a proximal forkhead box A1-binding site was critical for the AR-dependent activation of ELK4 promoter in prostate cancer cells. Preferential loading of holo-AR onto the ARE2 and concomitant recruitment of RNA polymerase II onto the ELK4 promoter was confirmed in prostate cancer cells by chromatin immunoprecipitation. Database searches indicated that the expression of ELK4 is markedly increased in prostate cancers relative to normal prostates. Moreover, prostate cancer tissue immunostainings showed that nuclear ELK4 levels are significantly increased in androgen-refractory prostate cancers compared to untreated tumours. Reduction of the amount of ELK4 in LNCaP cells by RNAi retarded cell growth. In conclusion, ELK4 is a direct AR target in prostate cancer cells. Androgens may thus contribute to the growth of prostate cancer via influencing ELK4 levels.

Use of xylanase and arabinofuranosidase for arabinose removal from unbleached kraft pulp.

Preparations of arabinofuranosidase and xylanase, respectively from Aureobasidium pullulans and Trichoderma longibrachiatum, were used to remove selectively xylose and arabinose from kraft pulp. The equilibrium moisture content of pulps treated with both enzymes, at varying relative humidities, revealed a consistently lower percent moisture content at all humidity set points. Shorter fiber lengths indicated some deterioration when pulp was exposed to high concentrations of both enzymes.

Histological characteristics of chronic hepatides and primary biliary cirrhosis with special reference to orcein positive hepatocellular accumulations.

The histological criteria of chronic hepatides (chronic persistent and aggressive hepatitis) and primary biliary cirrhosis are well characterized and documented in the literature. Histology forms the diagnostic basis for chronic hepatides. Diagnostic changes are seen, however, only in some cases of primary biliary cirrhosis (PBC) and only in the early stages of the disease. Difficulties are met especially in differentiating PBC from chronic aggressive hepatitis (CAH). There is a considerable histological overlap and mixed forms occur. Orcein-positive material, which is a copper-binding protein with high content of sulphydryl groups, accumulates in liver cells in long standing cholestatic liver diseases and can be demonstrated histochemically in routine biopsy specimens. It is seen in PBC in at least 70% of biopsy specimens which confirms the biliary nature of the disease. In CAH orcein positive material can be demonstrated in 20% of specimens but only from patients who also have features of PBC. This group of patients may therefore have both biliary disease are hepatocellular damage, and can be separated from CAH by the orcein method.

Clinical correlations and significance of orceinpositivity in chronic active hepatitis and primary biliary cirrhosis.

Clinical, biochemical and immunological variables were analyzed in 30 patients with orcein-negative (ON) chronic active hepatitis (CAH), 4 patients with ON primary biliary cirrhosis (PBC), 8 patients with orcein-positive (OP; intracellular copper-binding protein seen histologically in liver biopsy specimens) CAH and 15 patients with OP-PBC. A marked elevation of serum bile acids, alkaline phosphatase, leusine aminopeptidase, gammaglutamyl transpeptidase and cholesterol concentrations, and highly pathological BSP Tm values were characteristic for OP-cases. In addition the faecal fat level was increased and bile acids decreased in OP-cases. Serum levels of IgG or IgM and the occurrence of smooth muscle, mitochondrial or glomerular antibodies were identical in ON- and OP-CAH as well as also in ON- and OP-PBC. 49 patients were treated with a combination of prednisone and azathioprine from 4 to 72 months (mean 22). 26 patients with ON-CAH responded biochemically and morphologically to the treatment. No treatment failures were found in ON-CAH. In contrast treatment failure was confirmed in every treated OP-PBC or OP-CAH. The results suggest that orcein-positivity indicates a poor response to prednisone-azathioprine treatment of CAH.

The occurrence of orcein-positive hepatocellular material in various liver diseases.

Liver specimens from 103 patients with various hepatic diseases and from 297 consecutive liver biopsies examined routinely were stained with orcein after oxidation of the tissue sections with potassium permanganate. Orcein-positive dark brown cytoplasmic material could be demonstrated in 27 cases with long-standing cholestasis. These patients had either primary biliary cirrhosis, the cholestatic liver disease of ulcerative colitis or chronic active hepatitis, advanced alcoholic cirrhosis or secondary biliary cirrhosis due to extrahepatic biliary obstruction. Orcein-positive material could not be demonstrated in congenital disorders of bilirubin metabolism or in hemochromatosis. Similarly, it could not be found in acute, toxic, alcoholic or chronic persistent hepatitis.

Immunological parameters, viral antibodies, and biochemical and histological findings in relatives of patients with chronic active hepatitis and primary biliary cirrhosis.

The familial occurrence of immunological, virological, biochemical and histopathological abnormalities has been studied in 39 first degree relatives of patients with primary biliary cirrhosis (PBC) and in 58 first degree relatives of patients with chronic active hepatitis (CAH). Tissue antibodies were more frequent in relatives than in age- and sex-matched controls. Abnormal immunoglobulin levels were demonstrated in about half of the relatives. Very high antibody titres to measles and rubella occurred only in the relatives of the patients with CAH. Moreover the raised titres tended to be clustered in a few families in which also the propositi had very high viral antibody titres. Liver biopsy was performed only on the relatives with biochemical abnormalities. Unspecific inflammatory changes were observed in 5 relatives of the patients with CAH and in 4 relatives of the patients with PBC. An active liver disease was detected in two relatives of the PBC-group and in one of the CAH-group. A marked accumulation of various immunological and histopathological abnormalities in four families was observed.

Orcein positive hepatocellular material in histological diagnosis of primary biliary cirrhosis.

Liver biopsies from 18 patients with primary biliary cirrhosis (PBC) and from 25 patients with chronic active hepatitis (CAH) were stained by orcein after oxidation of the tissue sections with potassium permanganate. In 15 out of the 18 cases which could be classified on clinical, biochemical and immunological basis as PBC, the hepatocytes, usually periportally, contained cytoplasmic stainable material. 5 out of the 25 CAH patients contained the same material, but four of these patients were clinically atypical and showed features of cholestatic form of CAH and features crosslinking with PBC. All patients in both groups were serologically hepatitis-B antigen negative. The orcein staining method seems to be a reliable addition to differentiating histologically between PBC and CAH.