Recurrent, low-frequency coding variants contributing to colorectal cancer in the Swedish population

<div><p>Genome-wide association studies (GWAS) have identified dozens of common genetic variants associated with risk of colorectal cancer (CRC). However, the majority of CRC heritability remains unclear. In order to discover low-frequency, high-risk CRC susceptibility variants in Swedish population, we genotyped 1 515 CRC patients enriched for familial cases, and 12 108 controls. Case/control association analysis suggested eight novel variants associated with CRC risk (OR 2.0–17.6, p-value < 2.0E-07), comprised of seven coding variants in genes <i>RAB11FIP5</i>, <i>POTEA</i>, <i>COL27A1</i>, <i>MUC5B</i>, <i>PSMA8</i>, <i>MYH7B</i>, and <i>PABPC1L</i> as well as one variant downstream of <i>NEU1</i> gene. We also confirmed 27 out of 30 risk variants previously reported from GWAS in CRC with a mixed European population background. This study identified rare, coding sequence variants associated with CRC risk through analysis in a relatively homogeneous population. The segregation data suggest a complex mode of inheritance in seemingly dominant pedigrees.</p></div

Direct Identification of the Meloidogyne incognita Secretome Reveals Proteins with Host Cell Reprogramming Potential

The root knot nematode, Meloidogyne incognita, is an obligate parasite that causes significant damage to a broad range of host plants. Infection is associated with secretion of proteins surrounded by proliferating cells. Many parasites are known to secrete effectors that interfere with plant innate immunity, enabling infection to occur; they can also release pathogen-associated molecular patterns (PAMPs, e.g., flagellin) that trigger basal immunity through the nematode stylet into the plant cell. This leads to suppression of innate immunity and reprogramming of plant cells to form a feeding structure containing multinucleate giant cells. Effectors have generally been discovered using genetics or bioinformatics, but M. incognita is non-sexual and its genome sequence has not yet been reported. To partially overcome these limitations, we have used mass spectrometry to directly identify 486 proteins secreted by M. incognita. These proteins contain at least segmental sequence identity to those found in our 3 reference databases (published nematode proteins; unpublished M. incognita ESTs; published plant proteins). Several secreted proteins are homologous to plant proteins, which they may mimic, and they contain domains that suggest known effector functions (e.g., regulating the plant cell cycle or growth). Others have regulatory domains that could reprogram cells. Using in situ hybridization we observed that most secreted proteins were produced by the subventral glands, but we found that phasmids also secreted proteins. We annotated the functions of the secreted proteins and classified them according to roles they may play in the development of root knot disease. Our results show that parasite secretomes can be partially characterized without cognate genomic DNA sequence. We observed that the M. incognita secretome overlaps the reported secretome of mammalian parasitic nematodes (e.g., Brugia malayi), suggesting a common parasitic behavior and a possible conservation of function between metazoan parasites of plants and animals

Floral diversity during Plio-Pleistocene Siwalik sedimentation (Kimin Formation) in Arunachal Pradesh, India, and its palaeoclimatic significance

A morpho-taxonomic study of leaf remains from the upper part of the Siwalik succession of sediments (Kimin Formation; upper Pliocene to lower Pleistocene) of Papumpare district, Arunachal Pradesh, India, revealed 23 species representing 20 genera belonging to 15 angiosperm families. The recovered fossil leaves are comparable to modern Bambusa tulda Roxb. (Poaceae), Mangifera indica Linn., Dracontomelum mangiferum Blume (Anacardiaceae); Chonemorpha macrophylla G. Don (Apocynaceae); Pongamia pinnata (L) Pierre., Millettia pachycarpa Benth., Dalbergia rimosa Roxb., Millettia extensa (Fabaceae); Macaranga denticulate Muell. Arg., Croton caudatus Geisel. (Euphorbiaceae); Combretum decandrum Roxb. (Combretaceae); Dysoxylum procerum Hiern. (Meliaceae); Dipterocarpus sp. Gaertn.f. (Dipterocarpaceae); Actinodaphne angustifolia Nees., Actinodaphne obovata Blume., Lindera pulcherrima Benth., Litsea salicifolia Roxb. (Lauraceae); Calophyllum polyanthum Wall. (Clusiaceae); Knema glaucescens Hook.f. (Myristaceae); Canarium bengalense Roxb. (Burseraceae); Quercus lamellose Smith; Quercus semicarpifolia Smith (Fagaceae); and Berchemia floribunda Wall. (Rhamnaceae). Among these taxa, 11 species are recorded as new to the Neogene flora of India. Analysis of the floral assemblage with respect to the distribution pattern of modern equivalent taxa and the physiognomic characters of the fossil leaves, suggests that a tropical evergreen forest was growing in a warm humid climate in the region at the time of deposition. This is in contrast to modern tropical semi-evergreen forests that occupy the area. Values of mean annual temperature (MAT) of 29.3°C and mean annual precipitation (MAP) of 290 mm have been calculated using leaf-margin characters and fossil leaf size

Investigation of phonon coherence and backscattering using silicon nanomeshes

Phonons can display both wave-like and particle-like behaviour during thermal transport. While thermal transport in silicon nanomeshes has been previously interpreted by phonon wave effects due to interference with periodic structures, as well as phonon particle effects including backscattering, the dominant mechanism responsible for thermal conductivity reductions below classical predictions still remains unclear. Here we isolate the wave-related coherence effects by comparing periodic and aperiodic nanomeshes, and quantify the backscattering effect by comparing variable-pitch nanomeshes. We measure identical (within 6% uncertainty) thermal conductivities for periodic and aperiodic nanomeshes of the same average pitch, and reduced thermal conductivities for nanomeshes with smaller pitches. Ray tracing simulations support the measurement results. We conclude phonon coherence is unimportant for thermal transport in silicon nanomeshes with periodicities of 100 nm and higher and temperatures above 14 K, and phonon backscattering, as manifested in the classical size effect, is responsible for the thermal conductivity reduction