Individual tree traits shape insect and disease damage on oak in a climate‐matching tree diversity experiment

Diversifying planted forests by increasing genetic and species diversity is often promoted as a method to improve forest resilience to climate change and reduce pest and pathogen damage. In this study, we used a young tree diversity experiment replicated at two sites in the UK to study the impacts of tree diversity and tree provenance (geographic origin) on the oak (Quercus robur) insect herbivore community and a specialist biotrophic pathogen, oak powdery mildew. Local UK, French, and Italian provenances were planted in monocultures, provenance mixtures, and species mixes, allowing us to test whether: (a) local and nonlocal provenances differ in their insect herbivore and pathogen communities, and (b) admixing trees leads to associational effects on insect herbivore and pathogen damage. Tree diversity had variable impacts on foliar organisms across sites and years, suggesting that diversity effects can be highly dependent on environmental context. Provenance identity impacted upon both herbivores and powdery mildew, but we did not find consistent support for the local adaptation hypothesis for any group of organisms studied. Independent of provenance, we found tree vigor traits (shoot length, tree height) and tree apparency (the height of focal trees relative to their surroundings) were consistent positive predictors of powdery mildew and insect herbivory. Synthesis. Our results have implications for understanding the complex interplay between tree identity and diversity in determining pest damage, and show that tree traits, partially influenced by tree genotype, can be important drivers of tree pest and pathogen loads.     

ADP-dependent Conformational Changes Distinguish Mycobacterium tuberculosis SecA2 from SecA1

In bacteria, most secreted proteins are exported through the SecYEG translocon by the SecA ATPase motor via the general secretion or “Sec” pathway. The identification of an additional SecA protein, particularly in Gram-positive pathogens, has raised important questions about the role of SecA2 in both protein export and establishment of virulence. We previously showed in Mycobacterium tuberculosis, the causative agent of tuberculosis, the accessory SecA2 protein possesses ATPase activity that is required for bacterial survival in host macrophages, highlighting its importance in virulence. Here, we show that SecA2 binds ADP with much higher affinity than SecA1 and releases the nucleotide more slowly. Nucleotide binding also regulates movement of the precursor-binding domain in SecA2, unlike in SecA1 or conventional SecA proteins. This conformational change involving closure of the clamp in SecA2 may provide a mechanism for the cell to direct protein export through the conventional SecA1 pathway under normal growth conditions while preventing ordinary precursor proteins from interacting with the specialized SecA2 ATPase.     

The expanding roles of the Sd/Cad carbohydrate antigen and its cognate glycosyltransferase B4GALNT2

Background

The histo-blood group antigens are carbohydrate structures present in tissues and body fluids, which contribute to the definition of the individual immunophenotype. One of these, the Sd^a antigen, is expressed on the surface of erythrocytes and in secretions of the vast majority of the Caucasians and other ethnic groups.

Scope of review

We describe the multiple and unsuspected aspects of the biology of the Sd^a antigen and its biosynthetic enzyme β1,4-N-acetylgalactosaminyltransferase 2 (B4GALNT2) in various physiological and pathological settings.

Major conclusions

The immunodominant sugar of the Sd^a antigen is a β1,4-linked N-acetylgalactosamine (GalNAc). Its cognate glycosyltransferase B4GALNT2 displays a restricted pattern of tissue expression, is regulated by unknown mechanisms - including promoter methylation, and encodes at least two different proteins, one of which with an unconventionally long cytoplasmic portion. In different settings, the Sd^a antigen plays multiple and unsuspected roles. 1) In colon cancer, its dramatic down-regulation plays a potential role in the overexpression of sialyl Lewis antigens, increasing metastasis formation. 2) It is involved in the lytic function of murine cytotoxic T lymphocytes. 3) It prevents the development of muscular dystrophy in various dystrophic murine models, when overexpressed in muscular fibers. 4) It regulates the circulating half-life of the von Willebrand factor (vWf), determining the onset of a bleeding disorder in a murine model.

General significance

The expression of the Sd^a antigen has a wide impact on the physiology and the pathology of different biological systems.     

Sialosignaling: Sialyltransferases as engines of self-fueling loops in cancer progression

Background

Glycosylation is increasingly recognized as one of the most relevant postranslational modifications. Sialic acids are negatively charged sugars which frequently terminate the carbohydrate chains of glycoproteins and glycolipids. The addition of sialic acids is mediated by sialyltransferases, a family of glycosyltransferases with a crucial role in cancer progression.

Scope of the review

To describe the phenotypic and clinical implications of altered expression of sialyltransferases and of their cognate sialylated structures in cancer. To propose a unifying model of the role of sialyltransferases and sialylated structures on cancer progression.

Major conclusions

We first discuss the biosynthesis and the role played by the major cancer-associated sialylated structures, including Thomsen–Friedenreich-associated antigens, sialyl Lewis antigens, α2,6-sialylated lactosamine, polysialic acid and gangliosides. Then, we show that altered sialyltransferase expression in cancer, consequence of genetic and epigenetic alterations, generates a flow of information toward the membrane through the biosynthesis of aberrantly sialylated molecules (inside-out signaling). In turn, the presence of aberrantly sialylated structures on cell membrane receptors generates a flow of information toward the nucleus, which can exacerbate the neoplastic phenotype (outside-in signaling). We provide examples of self-fueling loops generated by these flows of information.

General significance

Sialyltransferases have a wide impact on the biology of cancer and can be the target of innovative therapies. Our unified view provides a conceptual framework to understand the impact of altered glycosylation in cancer.     

Lack of replication of higher genetic risk load in men than in women with systemic lupus erythematosus

Introduction

We aimed to replicate a recent study which showed higher genetic risk load at 15 loci in men than in women with systemic lupus erythematosus (SLE). This difference was very significant, and it was interpreted as indicating that men require more genetic susceptibility than women to develop SLE.

Methods

Nineteen SLE-associated loci (thirteen of which are shared with the previous study) were analyzed in 1,457 SLE patients and 1,728 healthy controls of European ancestry. Genetic risk load was calculated as sex-specific sum genetic risk scores (GRS_s).

Results

Our results did not replicate those of the previous study at either the level of individual loci or the global level of GRS_s. GRS_s were larger in women than in men (4.20 ± 1.07 in women vs. 3.27 ± 0.98 in men). This very significant difference (P < 10⁻¹⁶) was more dependent on the six new loci not included in the previous study (59% of the difference) than on the thirteen loci that are shared (the remaining 41%). However, the 13 shared loci also showed a higher genetic risk load in women than in men in our study (P = 6.6 × 10⁻⁷), suggesting that heterogeneity of participants, in addition to different loci, contributed to the opposite results.

Conclusion

Our results show the lack of a clear trend toward higher genetic risk in one of the sexes for the analyzed SLE loci. They also highlight several limitations of assessments of genetic risk load, including the possibility of ascertainment bias with loci discovered in studies that have included mainly women.