Mycoplasma feriruminatoris sp. nov., a fast growing Mycoplasma species isolated from wild Caprinae

Five Mycoplasma strains from wild Caprinae were analyzed: four from Alpine ibex (Capra ibex) which died at the Berlin Zoo between 1993 and 1994, one from a Rocky Mountain goat collected in the USA prior to 1987. These five strains represented a population different from the populations belonging to the 'Mycoplasma mycoides cluster' as tested using multi locus sequence typing, Matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis and DNA-DNA hybridization. Analysis of the 16S rRNA gene (rrs), genomic sequence based in silico as well as laboratory DNA-DNA hybridization, and the analysis of phenotypic traits in particular their exceptionally rapid growth all confirmed that they do not belong to any Mycoplasma species described to date. We therefore suggest these strains represent a novel species, for which we propose the name Mycoplasma feriruminatoris sp. nov. The type strain is G5847(T) (=DSM 26019(T)=NCTC 1362(T)).

Experimental adaptation of wild-type canine distemper virus (CDV) to the human entry receptor CD150.

Canine distemper virus (CDV), a close relative of measles virus (MV), is widespread and well known for its broad host range. When the goal of measles eradication may be achieved, and when measles vaccination will be stopped, CDV might eventually cross the species barrier to humans and emerge as a new human pathogen. In order to get an impression how fast such alterations may occur, we characterized required adaptive mutations to the human entry receptors CD150 (SLAM) and nectin-4 as first step to infect human target cells. Recombinant wild-type CDV-A75/17(red) adapted quickly to growth in human H358 epithelial cells expressing human nectin-4. Sequencing of the viral attachment proteins (hemagglutinin, H, and fusion protein, F) genes revealed that no adaptive alteration was required to utilize human nectin-4. In contrast, the virus replicated only to low titres (10(2) pfu/ml) in Vero cells expressing human CD150 (Vero-hSLAM). After three passages using these cells virus was adapted to human CD150 and replicated to high titres (10(5) pfu/ml). Sequence analyses revealed that only one amino acid exchange in the H-protein at position 540 Asp→Gly (D540G) was required for functional adaptation to human CD150. Structural modelling suggests that the adaptive mutation D540G in H reflects the sequence alteration from canine to human CD150 at position 70 and 71 from Pro to Leu (P70L) and Gly to Glu (G71E), and compensates for the gain of a negative charge in the human CD150 molecule. Using this model system our data indicate that only a minimal alteration, in this case one adaptive mutation, is required for adaptation of CDV to the human entry receptors, and help to understand the molecular basis why this adaptive mutation occurs.

Survey of bluetongue virus infection in free-ranging wild ruminants in Switzerland.

BACKGROUND In 2006, bluetongue virus serotype 8 (BTV-8) was detected for the first time in central Europe. Measures to control the infection in livestock were implemented in Switzerland but the question was raised whether free-ranging wildlife could be a maintenance host for BTV-8. Furthermore Toggenburg orbivirus (TOV), considered as a potential 25th BTV serotype, was detected in 2007 in domestic goats in Switzerland and wild ruminants were considered a potential source of infection. To assess prevalences of BTV-8 and TOV infections in wildlife, we conducted a serological and virological survey in red deer, roe deer, Alpine chamois and Alpine ibex between 2009 and 2011. Because samples originating from wildlife carcasses are often of poor quality, we also documented the influence of hemolysis on test results, and evaluated the usefulness of confirmatory tests. RESULTS Ten out of 1,898 animals (0.5%, 95% confidence interval 0.3-1.0%) had detectable antibodies against BTV-8 and BTV-8 RNA was found in two chamois and one roe deer (0.3%, 0.1-0.8%). Seroprevalence was highest among red deer, and the majority of positive wild animals were sampled close to areas where outbreaks had been reported in livestock. Most samples were hemolytic and the range of the optical density percentage values obtained in the screening test increased with increasing hemolysis. Confirmatory tests significantly increased specificity of the testing procedure and proved to be applicable even on poor quality samples. Nearly all samples confirmed as positive had an optical density percentage value greater than 50% in the ELISA screening. CONCLUSIONS Prevalence of BTV-8 infection was low, and none of the tested animals were positive for TOV. Currently, wild ruminants are apparently not a reservoir for these viruses in Switzerland. However, we report for the first time BTV-8 RNA in Alpine chamois. This animal was found at high altitude and far from a domestic outbreak, which suggests that the virus could spread into/through the Alps. Regarding testing procedures, hemolysis did not significantly affect test results but confirmatory tests proved to be necessary to obtain reliable prevalence estimates. The cut-off value recommended by the manufacturer for the screening test was applicable for wildlife samples.

Neoadjuvant chemoradiotherapy with or without panitumumab in patients with wild-type KRAS, locally advanced rectal cancer (LARC): a randomized, multicenter, phase II trial SAKK 41/07

BACKGROUND We conducted a randomized, phase II, multicenter study to evaluate the anti-epidermal growth factor receptor (EGFR) mAb panitumumab (P) in combination with chemoradiotherapy (CRT) with standard-dose capecitabine as neoadjuvant treatment for wild-type KRAS locally advanced rectal cancer (LARC). PATIENTS AND METHODS Patients with wild-type KRAS, T3-4 and/or N+ LARC were randomly assigned to receive CRT with or without P (6 mg/kg). The primary end-point was pathological near-complete or complete tumor response (pNC/CR), defined as grade 3 (pNCR) or 4 (pCR) histological regression by Dworak classification (DC). RESULTS Forty of 68 patients were randomly assigned to P + CRT and 28 to CRT. pNC/CR was achieved in 21 patients (53%) treated with P + CRT [95% confidence interval (CI) 36%-69%] versus 9 patients (32%) treated with CRT alone (95% CI: 16%-52%). pCR was achieved in 4 (10%) and 5 (18%) patients, and pNCR in 17 (43%) and 4 (14%) patients. In immunohistochemical analysis, most DC 3 cells were not apoptotic. The most common grade ≥3 toxic effects in the P + CRT/CRT arm were diarrhea (10%/6%) and anastomotic leakage (15%/4%). CONCLUSIONS The addition of panitumumab to neoadjuvant CRT in patients with KRAS wild-type LARC resulted in a high pNC/CR rate, mostly grade 3 DC. The results of both treatment arms exceeded prespecified thresholds. The addition of panitumumab increased toxicity.

High-resolution sequence stratigraphic correlation in the Upper Jurassic (Kimmeridgian)–Upper Cretaceous (Cenomanian) peritidal carbonate deposits (Western Taurides, Turkey)

Upper Jurassic (Kimmeridgian)±Upper Cretaceous (Cenomanian) inner platform carbonates in the Western Taurides are composed of metre-scale upward-shallowing cyclic deposits (parasequences) and important karstic surfaces capping some of the cycles. Peritidal cycles (shallow subtidal facies capped by tidal-¯at laminites or fenestrate limestones) are regressive- and transgressive-prone (upward-deepening followed by upward-shallowing facies trends). Subtidal cycles are of two types and indicate incomplete shallowing. Submerged subtidal cycles are composed of deeper subtidal facies overlain by shallow subtidal facies. Exposed subtidal cycles consist of deeper subtidal facies overlain by shallow subtidal facies that are capped by features indicative of prolonged subaerial exposure. Subtidal facies occur characteristically in the Jurassic, while peritidal cycles are typical for the Lower Cretaceous of the region. Within the foraminiferal and dasyclad algal biostratigraphic framework, four karst breccia levels are recognized as the boundaries of major second-order cycles, introduced for the ®rst time in this study. These levels correspond to the Kimmeridgian±Portlandian boundary, mid-Early Valanginian, mid-Early Aptian and mid-Cenomanian and represent important sea level falls which affected the distribution of foraminiferal fauna and dasyclad ¯ora of the Taurus carbonate platform. Within the Kimmeridgian±Cenomanian interval 26 third-order sequences (types 1 and 2) are recognized. These sequences are the records of eustatic sea level ¯uctuations rather than the records of local tectonic events because the boundaries of the sequences representing 1±4 Ma intervals are correlative with global sea level falls. Third-order sequences and metre-scale cyclic deposits are the major units used for long-distance, high-resolution sequence stratigraphic correlation in the Western Taurides. Metre-scale cyclic deposits (parasequences) in the Cretaceous show genetical stacking patterns within third-order sequences and correspond to fourth-order sequences representing 100±200 ka. These cycles are possibly the E2 signal (126 ka) of the orbital eccentricity cycles of the Milankovitch band. The slight deviation of values, calculated for parasequences, from the mean value of eccentricity cycles can be explained by the currently imprecise geochronology established in the Cretaceous and missed sea level oscillations when the platform lay above fluctuating sea level.

Sedimentary evolution and environmental history of Lake Van (Turkey) over the past 600,000 years

The lithostratigraphic framework of Lake Van, eastern Turkey, has been systematically analysed to document the sedimentary evolution and the environmental history of the lake during the past ca 600,000 years. The lithostratigraphy and chemostratigraphy of a 219 m long drill core from Lake Van serves to separate global climate oscillations from local factors caused by tectonic and volcanic activity. An age model was established based on the climatostratigraphic alignment of chemical and lithological signatures, validated by 40Ar/39Ar ages. The drilled sequence consists of ca 76% lacustrine carbonaceous clayey silt, ca 2% fluvial deposits, ca 17% volcaniclastic deposits and 5% gaps. Six lacustrine lithotypes were separated from the fluvial and event deposits, such as volcaniclastics (ca 300 layers) and graded beds (ca 375 layers), and their depositional environments are documented. These lithotypes are: (i) graded beds frequently intercalated with varved clayey silts reflect rising lake-levels during the terminations; (ii) varved clayey silts reflect strong seasonality and an intralake oxic–anoxic boundary, for example, lake-level highstands during interglacials/interstadials; (iii) CaCO3-rich banded sediments are representative of a lowering of the oxic-anoxic boundary, for example, lake-level decreases during glacial inceptions; (iv) CaCO3-poor banded and mottled clayey silts reflect an oxic–anoxic boundary close to the sediment-water interface, for example, lake-level low-stands during glacials/stadials; (v) diatomaceous muds were deposited during the early beginning of the lake as a fresh water system; and (vi) fluvial sands and gravels indicate the initial flooding of the lake basin. The recurrence of lithologies (i) to (iv) follows the past five glacial/interglacial cycles. A 20 m thick disturbed unit reflects an interval of major tectonic activity in Lake Van at ca 414 ka BP.

Wild pollinators enhance fruit set of crops regardless of honey bee abundance.

The diversity and abundance of wild insect pollinators have declined in many agricultural landscapes. Whether such declines reduce crop yields, or are mitigated by managed pollinators such as honey bees, is unclear. We found universally positive associations of fruit set with flower visitation by wild insects in 41 crop systems worldwide. In contrast, fruit set increased significantly with flower visitation by honey bees in only 14% of the systems surveyed. Overall, wild insects pollinated crops more effectively; an increase in wild insect visitation enhanced fruit set by twice as much as an equivalent increase in honey bee visitation. Visitation by wild insects and honey bees promoted fruit set independently, so pollination by managed honey bees supplemented, rather than substituted for, pollination by wild insects. Our results suggest that new practices for integrated management of both honey bees and diverse wild insect assemblages will enhance global crop yields.