The Invention of Propaganda

Prendergast, Maria Teresa Michaela; Prendergast, Thomas A.

doi:10.1093/oxfordhb/9780199764419.013.016

Cited by 8 publications

(9 citation statements)

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“…24,25 Accordingly, a large number of inhibitors, in particular those targeting hIDO1, have been developed. [34][35][36][37][38][39] Several frontline hIDO1 inhibitors, such as epacadostat, 40,41 PF-06840003 (IPD), 42 navoximod, 43,44 and BMS-986205, 45,46 have entered clinical trials. Among them, epacadostat and IPD stand out, as epacadostat is the most advanced inhibitor that shows unprecedented outcomes in both Phase I/II trials, 47,48 while IPD is the only inhibitor that is able to cross the blood-brain barrier.…”

Section: Introductionmentioning

confidence: 99%

Structural Basis of Inhibitor Selectivity in Human Indoleamine 2,3-Dioxygenase 1 and Tryptophan Dioxygenase

2019

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Indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan dioxygenase (hTDO) are two of the only three heme-based dioxygenases in humans. They have recently been identified as key cancer immunotherapeutic drug targets. While structures of hIDO1 in complex with inhibitors have been documented, so far there are no structures of hTDO-inhibitor complexes available. Here we use PF-06840003 (IPD), a hIDO1-selective inhibitor in clinical trials, as a structural probe to elucidate inhibitor-selectivity in hIDO1 versus hTDO. Spectroscopic studies show that IPD exhibits 400fold higher inhibition activity toward hIDO1 with respect to hTDO. Crystallographic structures reveal that the binding pocket of IPD in the active site in hIDO1 is much more flexible as compared to that in hTDO, which offers a molecular explanation for the superior inhibition activity of IPD in hIDO1 with respect to hTDO. In addition to the IPD bound in the active site, a second IPD molecule was identified in an inhibitory site on the proximal side of the heme in hIDO1 and in an exosite that is ~40 Å away from the active site in hTDO. Taken together the data provide new insights into structure-based design of mono and dual inhibitors targeting hIDO1 and/or hTDO.

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Section: Introductionmentioning

confidence: 99%

Structural Basis of Inhibitor Selectivity in Human Indoleamine 2,3-Dioxygenase 1 and Tryptophan Dioxygenase

2019

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“…5 In particular, the biomimetic 3D structures enabled by 3D printing could allow for the generation of in vitro tissue models that reproduce the physiology or pathophysiology of their in vivo niches. [6][7][8][9][10] The biomaterial matrixes provide multiple biological, structural, and mechanical supports in the regulation of cell behaviors and tissue morphogenesis, [11][12][13][14][15] while cells derived from individuals or patients allow for personalization of these microphysiological systems. 16,17 Conventionally, complex composite structures with hollow interiors reveal unique manufacturing challenges where internal tooling, 18 commonly referred to as a core or mandrel, is required to define the microchannel internal features.…”

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confidence: 99%

Generation of Cost-Effective Paper-Based Tissue Models through Matrix-Assisted Sacrificial 3D Printing

Cheng

Cao

et al. 2019

Nano Lett.

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Due to the combined advantages of cellulose and nanoscale (diameter 20-60 nm), bacterial cellulose possesses a series of attractive features including its natural origin, moderate biosynthesis process, good biocompatibility, and cost-effectiveness. Moreover, bacterial cellulose nanofibers can be conveniently processed into three-dimensional (3D) intertwined structures and form stable paper devices after simple drying. These advantages make it suitable as the material for construction of organ-on-a-chip devices using matrix-assisted sacrificial 3D printing. We successfully fabricated various microchannel structures embedded in the bulk bacterial cellulose hydrogels and retained their integrity after the drying process. Interestingly, these paper-based devices containing hollow microchannels could be rehydrated and populated with relevant cells to form vascularized tissue models. As a proof-of-concept demonstration, we seeded human

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“…In this small pilot feasibility study, exploratory analyses found that HEU infants exposed to household food insecurity had increased risk of stunting at birth compared to HUU infants whose mothers also reported food insecure conditions, suggesting that HEU infants may be more vulnerable to the programming effects of suboptimal nutrition in utero and postnatally than their HUU counterparts. Stunting is the most common manifestation of infant undernutrition globally [33], increasing morbidity and mortality in children in early life, and increasing one's risk of metabolic disease while reducing neurodevelopmental and economic capacity later in life [34]. Stunting is common amongst children living with HIV who are under 5 years and improves overtime with ART treatment [35], however, the extent to which HEU children are persistently at risk for stunting is not well understood.…”

Section: Discussionmentioning

confidence: 99%

How do maternal HIV infection and the early nutritional environment influence the development of infants exposed to HIVin utero?

White

Duffley

et al. 2019

Preprint

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Malnutrition and infectious disease often coexist in socially inequitable contexts. Malnutrition in the perinatal period adversely affects offspring development and lifelong non-communicable disease risk. Less is known about the effects of infectious disease exposure during critical windows of development and health, and links between in utero HIV-exposure in the absence of neonatal infection, perinatal nutritional environments, and infant development are poorly defined. In a pilot feasibility study at Kalafong Hospital, Pretoria, South Africa, we aimed to better understand relationships between maternal HIV infection and the early nutritional environment of in utero HIV exposed uninfected (HEU) infants. We also undertook exploratory analyses to investigate relationships between food insecurity and infant development. Mother-infant dyads were recruited after delivery and followed until 12 weeks postpartum. Household food insecurity, nutrient intakes and dietary diversity scores did not differ between mothers living with or without HIV. Maternal reports of food insecurity were associated with lower maternal nutrient intakes 12 weeks postpartum, and in infants, higher brain-to-body weight ratio at birth and 12 weeks of age, and attainment of fewer large movement and play activities milestones at 12 weeks of age, irrespective of maternal HIV status. Reports of worry about food runout were associated with increased risk of stunting for HEU, but not unexposed, uninfected infants. Our findings suggest that food insecurity, in a vulnerable population, adversely affects maternal nutritional status and infant development. In utero exposure to HIV may further perpetuate these effects, which has implications for early child development and lifelong human capital.

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The Invention of Propaganda

Cited by 8 publications

References 0 publications

Structural Basis of Inhibitor Selectivity in Human Indoleamine 2,3-Dioxygenase 1 and Tryptophan Dioxygenase

Structural Basis of Inhibitor Selectivity in Human Indoleamine 2,3-Dioxygenase 1 and Tryptophan Dioxygenase

Generation of Cost-Effective Paper-Based Tissue Models through Matrix-Assisted Sacrificial 3D Printing

How do maternal HIV infection and the early nutritional environment influence the development of infants exposed to HIVin utero?

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