Partnering with the Old Order Mennonites in the Finger Lakes Region of New York State to Identify the Mechanisms of Protective Immunity Against Atopic Disease Development

Old Order Mennonites (OOM) follow a traditional agrarian lifestyle; key aspects include home births, large families, limited antibiotic usage, consumption of whole foods and unpasteurized milk, and early exposure to soil, stables, and farm animals. There is evidence that a farming lifestyle protects against asthma and allergies, yet the biological mechanisms behind this protective effect remain unknown. The “Zooming into Old Order Mennonites” (ZOOM) cohort study was established to further explore protective factors and mechanisms. This study compares immune development among OOM children from the Finger Lakes Region of New York to those residing 65 miles northwest in Rochester, NY. Participants completed prenatal and post-natal questionnaires and biomarker sampling throughout the infant’s first two years. Questionnaires on lifestyle, diet, and environmental exposures continued through year five. The success of this study depended on a partnership between the University of Rochester study team and the OOM community, which began in 2009 with a pilot study on prenatal lifestyle behaviors and environmental exposures. Since then, the study team and the OOM community have collaborated to investigate the prevalence and mechanisms underlying atopic disease. The study team has remained mindful of OOM cultural practices by carefully engaging community members and potential participants through key informant interviews, focus groups, and “town hall” data-sharing meetings. To truly respect this community, they must be involved at every step of the research process. Through these efforts, the ZOOM study team recruited 90 OOM mother-infant pairs. Ultimately, this study marks a step closer to preventing allergic disease. [Abstract by authors.

Quantitative glycoproteomics of human milk and association with atopic disease

The prevalence of allergic diseases and asthma is increasing rapidly worldwide, with environmental and lifestyle behaviors implicated as a reason. Epidemiological studies have shown that children who grow up on farms are at lower risk of developing childhood atopic disease, indicating the presence of a protective "farm effect". The Old Order Mennonite (OOM) community in Upstate New York have traditional, agrarian lifestyles, a low rate of atopic disease, and long periods of exclusive breastfeeding. Human milk proteins are heavily glycosylated, although there is a paucity of studies investigating the milk glycoproteome. In this study, we have used quantitative glycoproteomics to compare the N-glycoprotein profiles of 54 milk samples from Rochester urban/suburban and OOM mothers, two populations with different lifestyles, exposures, and risk of atopic disease. We also compared N-glycoprotein profiles according to the presence or absence of atopic disease in the mothers and, separately, the children. We identified 79 N-glycopeptides from 15 different proteins and found that proteins including immunoglobulin A1, polymeric immunoglobulin receptor, and lactotransferrin displayed significant glycan heterogeneity. We found that the abundances of 38 glycopeptides differed significantly between Rochester and OOM mothers and also identified four glycopeptides with significantly different abundances between all comparisons. These four glycopeptides may be associated with the development of atopic disease. The findings of this study suggest that the differential glycosylation of milk proteins could be linked to atopic disease.Peer reviewe

Sepsis promotes splenic production of a protective platelet pool with high CD40 ligand expression.

Platelets have a wide range of functions including critical roles in hemostasis, thrombosis, and immunity. We hypothesized that during acute inflammation, such as in life-threatening sepsis, there are fundamental changes in the sites of platelet production and phenotypes of resultant platelets. Here, we showed during sepsis that the spleen was a major site of megakaryopoiesis and platelet production. Sepsis provoked an adrenergic-dependent mobilization of megakaryocyte-erythrocyte progenitors (MEPs) from the bone marrow to the spleen, where IL-3 induced their differentiation into megakaryocytes (MKs). In the spleen, immune-skewed MKs produced a CD40 ligandhi platelet population with potent immunomodulatory functions. Transfusions of post-sepsis platelets enriched from splenic production enhanced immune responses and reduced overall mortality in sepsis-challenged animals. These findings identify a spleen-derived protective platelet population that may be broadly immunomodulatory in acute inflammatory states such as sepsis.NHS Blood and Transplant European Union's Horizon 2020 (ERC-2014-CoG-648765) MRC-AMED (MR/V005421/1

The VLA/ALMA Nascent Disk and Multiplicity (VANDAM) Survey of Orion Protostars. IV. Unveiling the Embedded Intermediate-Mass Protostar and Disk within OMC2-FIR3/HOPS-370

We present ALMA (0.87 and 1.3 mm) and VLA (9 mm) observations toward the candidate intermediate-mass protostar OMC2-FIR3 (HOPS-370; L_(bol) ~ 314 L_⊙) at ~0."1 (40 au) resolution for the continuum emission and ~0."25 (100 au) resolution of nine molecular lines. The dust continuum observed with ALMA at 0.87 and 1.3 mm resolves a near edge-on disk toward HOPS-370 with an apparent radius of ~100 au. The VLA observations detect both the disk in dust continuum and free–free emission extended along the jet direction. The ALMA observations of molecular lines (H₂CO, SO, CH₃OH, ¹³CO, C¹⁸O, NS, and H¹³CN) reveal rotation of the apparent disk surrounding HOPS-370 orthogonal to the jet/outflow direction. We fit radiative transfer models to both the dust continuum structure of the disk and molecular line kinematics of the inner envelope and disk for the H₂CO, CH₃OH, NS, and SO lines. The central protostar mass is determined to be ~2.5 M_⊙ with a disk radius of ~94 au, when fit using combinations of the H₂CO, CH₃OH, NS, and SO lines, consistent with an intermediate-mass protostar. Modeling of the dust continuum and spectral energy distribution yields a disk mass of 0.035 M_⊙ (inferred dust+gas) and a dust disk radius of 62 au; thus, the dust disk may have a smaller radius than the gas disk, similar to Class II disks. In order to explain the observed luminosity with the measured protostar mass, HOPS-370 must be accreting at a rate of (1.7−3.2) × 10⁻⁵ M_⊙ yr⁻¹

The Critical Juncture Concept’s Evolving Capacity to Explain Policy Change

This article examines the evolution of our understanding of the critical junctures concept. The concept finds its origins in historical intuitionalism, being employed in the context of path dependence to account for sudden and jarring institutional or policy changes. We argue that the concept and the literature surrounding it—now incorporating ideas, discourse, and agency—have gradually become more comprehensive and nuanced as historical institutionalism was followed by ideational historical institutionalism and constructivist and discursive institutionalism. The prime position of contingency has been supplanted by the role of ideas and agency in explaining critical junctures and other instances of less than transformative change. Consequently, the concept is now capable of providing more comprehensive explanations for policy change