Identification of Novel Candidate Genes for Early-Onset Colorectal Cancer Susceptibility

Approximately 25–30% of colorectal cancer (CRC) cases are expected to result from a genetic predisposition, but in only 5–10% of these cases highly penetrant germline mutations are found. The remaining CRC heritability is still unexplained, and may be caused by a hitherto-undefined set of rare variants with a moderately penetrant risk. Here we aimed to identify novel risk factors for early-onset CRC using whole-exome sequencing, which was performed on a cohort of CRC individuals (n = 55) with a disease onset before 45 years of age. We searched for genes that were recurrently affected by rare variants (minor allele frequency ≤0.001) with potentially damaging effects and, subsequently, re-sequenced the candidate genes in a replication cohort of 174 early-onset or familial CRC individuals. Two functionally relevant genes with low frequency variants with potentially damaging effects, PTPN12 and LRP6, were found in at least three individuals. The protein tyrosine phosphatase PTP-PEST, encoded by PTPN12, is a regulator of cell motility and LRP6 is a component of the WNT-FZD-LRP5-LRP6 complex that triggers WNT signaling. All variants in LRP6 were identified in individuals with an extremely early-onset of the disease (≤30 years of age), and two of the three variants showed increased WNT signaling activity in vitro. In conclusion, we present PTPN12 and LRP6 as novel candidates contributing to the heterogeneous susceptibility to CRC.     

Insect pathological investigations on Swedish thysanura: Observations on Malamoeba locustae (Protozoa,Amoebidae) from Lepisma saccharina (Thysanura,Lepismatidae)

A case of spontaneous infection of Malamoeba locustae from a free-living indoor population of Lepisma saccharina is reported. The source of infection was probably a culture of Schistocerca gregaria reared in the same room. Measurements of fixed cysts from L. saccharina are compared with measurements of fixed and unfixed cysts from S. gregaria and with published data from other species of grasshoppers and locusts.     

Intrafloral patterns of color and scent in Capparis spinosa L. and the ghosts of its selection past

Premise

Capparis spinosa is a widespread charismatic plant, in which the nocturnal floral habit contrasts with the high visitation by diurnal bees and the pronounced scarcity of hawkmoths. To resolve this discrepancy and elucidate floral evolution of C. spinosa, we analyzed the intrafloral patterns of visual and olfactory cues in relation to the known sensory biases of the different visitor guilds (bees, butterflies, and hawkmoths).

Methods

We measured the intrafloral variation of scent, reflectance spectra, and colorimetric properties according to three guilds of known visitors of C. spinosa. Additionally, we sampled visitation rates using a motion-activated camera.

Results

Carpenter bees visited the flowers eight times more frequently than nocturnal hawkmoths, at dusk and in the following morning. Yet, the floral headspace of C. spinosa contained a typical sphingophilous scent with high emission rates of certain monoterpenes and amino-acid derived compounds. Visual cues included a special case of multisensory nectar guide and color patterns conspicuous to the visual systems of both hawkmoths and bees.

Conclusions

The intrafloral patterns of sensory stimuli suggest that hawkmoths have exerted strong historical selection on C. spinosa. Our study revealed two interesting paradoxes: (a) the flowers phenotypically biased towards the more inconsistent pollinator; and (b) floral display demands an abundance of resources that seems maladaptive in the habitats of C. spinosa. The transition to a binary pollination system accommodating large bees has not required phenotypic changes, owing to specific eco-physiological adaptations, unrelated to pollination, which make this plant an unusual case in pollination ecology.     

Decoding the drivers of deep-time wetland biodiversity: insights from an early Permian tropical lake ecosystem

Wetlands are important to continental evolution, providing both arenas and refugia for emerging and declining biotas. This significance and the high preservation potential make the resulting fossiliferous deposits essential for our understanding of past and future biodiversity. We reconstruct the trophic structure and age of the early Permian Manebach Lake ecosystem, Germany, a thriving wetland at a time when the tropical biosphere faced profound upheaval in the peaking Late Palaeozoic Icehouse. Nine excavations, high-resolution spatiotemporal documentation of fossils and strata, and U–Pb radioisotopic dating of tuffs allow us to distinguish autogenic and allogenic factors shaping the limnic biocoenosis. The Manebach Lake was an exorheic, oxygen-stratified, perennial water body on the 10¹–10² km² scale, integrated into the catchment draining much of the European Variscides. Lake formation paralleled an Asselian regional wet climatic interval and benefited from rising base level due to post-Variscan half-graben tectonics. Stromatolite-forming cyanobacteria, bivalves, several crustaceans, amblypterids and xenacanthid sharks formed a differentiated biocoenosis in the lake. Fossil stomach remains and teeth prove the rare presence of acanthodians, branchiosaurs and large amphibians. The results indicate woody-debris-bearing lake littorals devoid of semi-aquatic and aquatic plants as places suitable for stromatolites to grow, underpin the model of declining freshwater-shark diversity in most Permian Variscan basins, demonstrate fish/amphibian ratios in limnic assemblages to measure lake perenniality and reveal taphonomic biases in lake taphocoenoses. Our outcomes call for more knowledge about the diversity, ecology and fossilization pathways of past limnic biotas, particularly microorganisms and actinopterygian fishes, to reconstruct deep-time continental ecosystems.     

Comparison of methods for the analysis of therapeutic immunoglobulin G Fc-glycosylation profiles—Part 1: Separation-based methods

Immunoglobulin G (IgG) crystallizable fragment (Fc) glycosylation is crucial for antibody effector functions, such as antibody-dependent cell-mediated cytotoxicity, and for their pharmacokinetic and pharmacodynamics behavior. To monitor the Fc-glycosylation in bioprocess development, as well as product characterization and release analytics, reliable techniques for glycosylation analysis are needed. A wide range of analytical methods has found its way into these applications. In this study, a comprehensive comparison was performed of separation-based methods for Fc-glycosylation profiling of an IgG biopharmaceutical. A therapeutic antibody reference material was analyzed 6-fold on 2 different days, and the methods were compared for precision, accuracy, throughput and other features; special emphasis was placed on the detection of sialic acid-containing glycans. Seven, non-mass spectrometric methods were compared; the methods utilized liquid chromatography-based separation of fluorescent-labeled glycans, capillary electrophoresis-based separation of fluorescent-labeled glycans, or high-performance anion exchange chromatography with pulsed amperometric detection. Hydrophilic interaction liquid chromatography-ultra high performance liquid chromatography of 2-aminobenzamide (2-AB)-labeled glycans was used as a reference method. All of the methods showed excellent precision and accuracy; some differences were observed, particularly with regard to the detection and quantitation of minor glycan species, such as sialylated glycans.