A Functional Role for Antibodies in Tuberculosis.

While a third of the world carries the burden of tuberculosis, disease control has been hindered by a lack of tools, including a rapid, point-of-care diagnostic and a protective vaccine. In many infectious diseases, antibodies (Abs) are powerful biomarkers and important immune mediators. However, in Mycobacterium tuberculosis (Mtb) infection, a discriminatory or protective role for humoral immunity remains unclear. Using an unbiased antibody profiling approach, we show that individuals with latent tuberculosis infection (Ltb) and active tuberculosis disease (Atb) have distinct Mtb-specific humoral responses, such that Ltb infection is associated with unique Ab Fc functional profiles, selective binding to FcγRIII, and distinct Ab glycosylation patterns. Moreover, compared to Abs from Atb, Abs from Ltb drove enhanced phagolysosomal maturation, inflammasome activation, and, most importantly, macrophage killing of intracellular Mtb. Combined, these data point to a potential role for Fc-mediated Ab effector functions, tuned via differential glycosylation, in Mtb control.

Developmental and molecular characterization of novel staminodes in Aquilegia.

BACKGROUND AND AIMS: The ranunculid model system Aquilegia is notable for the presence of a fifth type of floral organ, the staminode, which appears to be the result of sterilization and modification of the two innermost whorls of stamens. Previous studies have found that the genetic basis for the identity of this new organ is the result of sub- and neofunctionalization of floral organ identity gene paralogues; however, we do not know the extent of developmental and molecular divergence between stamens and staminodes. METHODS: We used histological techniques to describe the development of the Aquilegia coerulea 'Origami' staminode relative to the stamen filament. These results have been compared with four other Aquilegia species and the closely related genera Urophysa and Semiaquilegia. As a complement, RNA sequencing has been conducted at two developmental stages to investigate the molecular divergence of the stamen filaments and staminodes in A. coerulea 'Origami'. KEY RESULTS: Our developmental study has revealed novel features of staminode development, most notably a physical interaction along the lateral margin of adjacent organs that appears to mediate their adhesion. In addition, patterns of abaxial/adaxial differentiation are observed in staminodes but not stamen filaments, including asymmetric lignification of the adaxial epidermis in the staminodes. The comparative transcriptomics are consistent with the observed lignification of staminodes and indicate that stamen filaments are radialized due to overexpression of adaxial identity, while the staminodes are expanded due to the balanced presence of abaxial identity. CONCLUSIONS: These findings suggest a model in which the novel staminode identity programme interacts with the abaxial/adaxial identity pathways to produce two whorls of laterally expanded organs that are highly differentiated along their abaxial/adaxial axis. While the ecological function of Aquilegia staminodes remains to be determined, these data are consistent with a role in protecting the early carpels from herbivory and/or pathogens.

Psychiatric polygenic risk scores: Experience, hope for utility, and concerns among child and adolescent psychiatrists.

Recent advances in psychiatric genetics have enabled the use of polygenic risk scores (PRS) to estimate genetic risk for psychiatric disorders. However, the potential use of PRS in child and adolescent psychiatry has raised concerns. This study provides an in-depth examination of attitudes among child and adolescent psychiatrists (CAP) regarding the use of PRS in psychiatry. We conducted semi-structured interviews with U.S.-based CAP (n = 29) who possess expertise in genetics. The majority of CAP indicated that PRS have limited clinical utility in their current form and are not ready for clinical implementation. Most clinicians stated that nothing would motivate them to generate PRS at present; however, some exceptions were noted (e.g., parent/family request). Clinicians spoke to challenges related to ordering, interpreting, and explaining PRS to patients and families. CAP raised concerns regarding the potential for this information to be misinterpreted or misused by patients, families, clinicians, and outside entities such as insurance companies. Finally, some CAP noted that PRS may lead to increased stigmatization of psychiatric disorders, and at the extreme, could be used to support eugenics. As PRS testing increases, it will be critical to examine CAP and other stakeholders' views to ensure responsible implementation of this technology.