Type I Interferons Link Viral Infection to Enhanced Epithelial Turnover and Repair

The host immune system functions constantly to maintain chronic commensal and pathogenic organisms in check. The consequences of these immune responses on host physiology are as yet unexplored, and may have long-term implications in health and disease. We show that chronic viral infection increases epithelial turnover in multiple tissues, and the antiviral cytokines type I interferons (IFNs) mediate this response. Using a murine model with persistently elevated type I IFNs in the absence of exogenous viral infection, the Irgm1−/− mouse, we demonstrate that type I IFNs act through nonepithelial cells, including macrophages, to promote increased epithelial turnover and wound repair. Downstream of type I IFN signaling, the highly related IFN-stimulated genes Apolipoprotein L9a and b activate epithelial proliferation through ERK activation. Our findings demonstrate that the host immune response to chronic viral infection has systemic effects on epithelial turnover through a myeloid-epithelial circuit

Was it Uruguay or Coffee? The causes of the beef jerky industry’s decline in southern Brazil (1850 – 1889)

What caused the decline of the beef jerky’s production in Brazil? The main sustenance for slaves, beef jerky was the most important industry in southern Brazil. Nevertheless, by 1850, producers were already worried that they could not compete with Uruguayan industry. Traditional interpretations impute the decline to labor markets differences in productivity, since Brazil used slaves while Uruguay had abolished slavery in 1842. Recent research also raises the possibility of a Brazilian “Dutch Disease”, resulting from the coffee exports boom. We test both hypothesis and argue that Brazilian production’s decline was associated with structural changes in demand for low quality meat. Trade protection policies created disincentives for Brazilian producers to increase productivity and diversify its cattle industry

Occupational variation in the relationship between child health and family size

Empirical evidence for quantity‐quality trade‐off is hardly ubiquitous, especially when quality is measured by child health outcomes. The paper offers a new explanation to this puzzle. It shows that the quantity–quality relationships are subject to occupational variation when quality is given by nutritional status, and occupations differ in their physical labor intensity. It embeds, in a simple household optimization model, a minimum consumption requirement that rises with physical work intensity of occupation. The occupational differences in subsistence consumption requirement generate variation in child nutritional status, and hence, in the shadow price of children. The nature of the quantity–quality relationship, therefore, varies with work intensity of occupations. The model yields an equilibrium relationship between the number and nutritional status of children that is positive for households in strenuous occupations and ambiguous for other households. These results help reconcile some inconsistent findings on quantity–quality trade‐off, which may partly be explained by the omission of occupational variation in nutritional status

Mutation of senataxin alters disease-specific transcriptional networks in patients with ataxia with oculomotor apraxia type 2

Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional role of senataxin in disease, we examined differential gene expression in AOA2 patient fibroblasts, identifying a core set of genes showing altered expression by microarray and RNA-sequencing. To determine whether AOA2 and ALS4 mutations differentially affect gene expression, we overexpressed disease-specific SETX mutations in senataxin-haploinsufficient fibroblasts and observed changes in distinct sets of genes. This implicates mutation-specific alterations of senataxin function in disease pathogenesis and provides a novel example of allelic neurogenetic disorders with differing gene expression profiles. Weighted gene co-expression network analysis (WGCNA) demonstrated these senataxin-associated genes to be involved in both mutation-specific and shared functional gene networks. To assess this in vivo, we performed gene expression analysis on peripheral blood from members of 12 different AOA2 families and identified an AOA2-specific transcriptional signature. WGCNA identified two gene modules highly enriched for this transcriptional signature in the peripheral blood of all AOA2 patients studied. These modules were disease-specific and preserved in patient fibroblasts and in the cerebellum of Setx knockout mice demonstrating conservation across species and cell types, including neurons. These results identify novel genes and cellular pathways related to senataxin function in normal and disease states, and implicate alterations in gene expression as underlying the phenotypic differences between AOA2 and ALS4

Impact of Obstructive Sleep Apnea on Insulin Resistance and Glucose Tolerance in Women with Polycystic Ovary Syndrome

Context: Insulin resistance, impaired glucose tolerance, and type 2 diabetes are common in women with polycystic ovary syndrome (PCOS). Obstructive sleep apnea (OSA) has been linked to metabolic dysfunction. We studied women with and without PCOS to determine the extent to which OSA is responsible for insulin resistance and glucose intolerance in PCOS