Extraintestinal pathogenic <i>Escherichia coli</i> are associated with intestinal inflammation in patients with ulcerative colitis

E. coli of the phylogenetic group B2 harbouring Extra intestinal Pathogenic Escherichia coli (ExPEC) genes are frequently seen as colonizers of the intestine in patients with active ulcerative colitis (UC). In this study, we describe the influence of E. coli Nissle (EcN) B2 as add-on treatment to conventional therapies in patients with active UC. For this study one hundred active UC patients were randomized to ciprofloxacin or placebo for 1 week followed by EcN or placebo for 7 weeks. Stool samples were collected at weeks 0, 1, 8, 12, where E. coli were characterized and fecal calprotectin was measured. We showed that in the active UC patient group receiving Placebo/EcN, fewer patients reached remission, in comparison to the patient group receiving Placebo/placebo (p < 0.05). Active UC patients initially colonized with E. coli B2 had increased fecal calprotectin values and Colitis Activity Index scores in comparison to patients colonized with E. coli A and D (p < 0.05*). In conclusion, treatment of UC patients with E. coli Nissle (B2) does not promote clinical remission and active UC patients colonized with E. coli B2 have an increased intestinal inflammation

Beringian paleoecology inferred from permafrost-preserved fungal DNA

The diversity of fungi in permanently frozen soil from northeastern Siberia was studied by culture-independent PCR amplification of diverse environmental 18S rRNA genes. Elaborate protocols to avoid contamination during drilling, sampling, and amplification were used. A broad diversity of eukaryotic DNA sequences that were 510 bp long, including sequences of various fungi, plants, and invertebrates, could be obtained reproducibly from samples that were up to 300,000 to 400,000 years old. The sequences revealed that ancient fungal communities included a diversity of cold-adapted yeasts, dark-pigmented fungi, plant-parasitic fungi, and lichen mycobionts. DNA traces of tree-associated macrofungi in a modern tundra sample indicated that there was a shift in fungal diversity following the last ice age and supported recent results showing that there was a severe change in the plant composition in northeastern Siberia during this period. Interestingly, DNA sequences with high homology to sequences of coprophilic and keratinophilic fungi indicated that feces, hair, skin, and nails could have been sources of ancient megafauna DNA recently reported to be present in small amounts of Siberian permafrost sediments

Heparan sulfate regulates ADAM12 through a molecular switch mechanism.

International audienceThe disintegrin and metalloproteases (ADAMs) are emerging as therapeutic targets in human disease, but specific drug design is hampered by potential redundancy. Unlike other metzincins, ADAM prodomains remain bound to the mature enzyme to regulate activity. Here ADAM12, a protease that promotes tumor progression and chondrocyte proliferation in osteoarthritic cartilage, is shown to possess a prodomain/catalytic domain cationic molecular switch, regulated by exogenous heparan sulfate and heparin but also endogenous cell surface proteoglycans and the polyanion, calcium pentosan polysulfate. Sheddase functions of ADAM12 are regulated by the switch, as are proteolytic functions in placental tissue and sera of pregnant women. Moreover, human heparanase, an enzyme also linked to tumorigenesis, can promote ADAM12 sheddase activity at the cell surface through cleavage of the inhibitory heparan sulfate. These data present a novel concept that might allow targeting of ADAM12 and suggest that other ADAMs may have specific regulatory activity embedded in their prodomain and catalytic domain structures

GAD65 autoantibodies and glucose tolerance in offspring born to women with and without type 1 diabetes (The EPICOM study)

The aims of this study were to examine presence of GAD65 autoantibodies (GAD65aab) in offspring born to women with type 1 diabetes (T1D) and controls and if more were GAD65aab‐positive if diagnosed with diabetes or pre‐diabetes. This EPICOM study is a prospective follow‐up study focussing on pregnancies complicated by maternal T1D. The EPICOM study includes offspring (n = 278) born to mothers with pre‐gestational T1D between 1993 and 1999 and matched un‐exposed controls (n = 303). Age at the time of follow‐up was 16.7 years (13.0–20.4 years). GAD65aab was measured using the Glutamic Acid Decarboxylase Autoantibody RIA kit from RSR(©). An Oral Glucose Tolerance Test (OGTT) was performed, and abnormal glucose tolerance was defined as having either diabetes, impaired fasting glucose (IFG) or impaired glucose tolerance (IGT). GAD65aab could be measured in 561 participants. Of these, 17 (3%) were positive for GAD65aab (≥25 U/ml) with 11 (4%) offspring being born to women with T1D and 6 (2%) controls. The difference in GAD65aab status was not statistically significant (p = .2). One was diagnosed with GAD65aab‐negative diabetes during the study, 18 were diagnosed with IFG, and 44 with IGT. Overall, more were GAD65aab‐positive if diagnosed with abnormal glucose tolerance (p = .03). We found no association between GAD65aab status and HOMA‐IR, HOMA‐IS, birthweight, mode of delivery or maternal BMI prior to pregnancy. Our study found no overall difference in GAD65 status between offspring born to women with T1D and their matched controls. However, among the participants diagnosed with pre‐diabetes more were GAD65‐positive

Characteristics of SLE patients and healthy controls.

<p>SLE—systemic lupus erythematosus, SLEDAI—SLE disease activity index, ANA- nuclear antibodies, dsDNA—double stranded DNA, Ig—immunoglobulin, eGFR—estimated glomerular filtration rate, ND—not determined.</p><p>Characteristics of SLE patients and healthy controls.</p

No correlation between SLEDAI scores and total immunoglobulin concentrations in SLE patients.

<p>No correlation between SLEDAI scores and total IgG, IgA and IgM in SLE patients (n = 45) with r-values of 0.247 (p = 0.102), 0.175 (p = 0.250) and 0.116 (p = 0.316) regarding total IgG, IgA and IgM, respectively. SLEDAI—systemic lupus erythematosus disease activity index.</p

Correlation between serum FLC concentrations and anti-dsDNA titer.

<p>Correlation between anti-dsDNA titer (U/ml) and total FLC (A), λFLC (B) and κFLC (C) levels in SLE patients (n = 45). r-values are 0.383 (p = 0.009), 0.369 (p = 0.013) and 0.401 (p = 0.006) in A, B and C, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus, dsDNA—double stranded DNA.</p

Correlation between serum FLC concentrations and total immunoglobulin levels.

<p>Correlation between total immunoglobulin levels and total FLC, λFLC and κFLC levels in SLE patients (A) (n = 45) and healthy controls (B) (n = 40) <b>A: SLE patients</b>. r-values are 0.345 (p = 0.021), 0.499 (p = 0.0005) and -0.127 (p = 0.406) regarding total FLC, λFLC and κFLC levels, respectively. <b>B: Healthy controls</b>. r-values are 0.301 (p = 0.059), 0.377 (p = 0.016) and -0.268 (p = 0.094) regarding total FLC, λFLC and κFLC levels, respectively. FLCs—free light chains, SLE—systemic lupus erythematosus.</p