Atherosusceptible Shear Stress Activates Endoplasmic Reticulum Stress to Promote Endothelial Inflammation.

Atherosclerosis impacts arteries where disturbed blood flow renders the endothelium susceptible to inflammation. Cytokine activation of endothelial cells (EC) upregulates VCAM-1 receptors that target monocyte recruitment to atherosusceptible regions. Endoplasmic reticulum (ER) stress elicits EC dysregulation in metabolic syndrome. We hypothesized that ER plays a central role in mechanosensing of atherosusceptible shear stress (SS) by signaling enhanced inflammation. Aortic EC were stimulated with low-dose TNFα (0.3 ng/ml) in a microfluidic channel that produced a linear SS gradient over a 20mm field ranging from 0-16 dynes/cm2. High-resolution imaging of immunofluorescence along the monolayer provided a continuous spatial metric of EC orientation, markers of ER stress, VCAM-1 and ICAM-1 expression, and monocyte recruitment. VCAM-1 peaked at 2 dynes/cm2 and decreased to below static TNFα-stimulated levels at atheroprotective-SS of 12 dynes/cm2, whereas ICAM-1 rose to a maximum in parallel with SS. ER expansion and activation of the unfolded protein response also peaked at 2 dynes/cm2, where IRF-1-regulated VCAM-1 expression and monocyte recruitment also rose to a maximum. Silencing of PECAM-1 or key ER stress genes abrogated SS regulation of VCAM-1 transcription and monocyte recruitment. We report a novel role for ER stress in mechanoregulation at arterial regions of atherosusceptible-SS inflamed by low-dose TNFα

Preface to SSL 42:1

Introduces the two special sections in this issue, on Scottish fiction and Burns bibliography, and briefly describes the range of other contributions, noting the wide international range of contributors

Preface to SSL 41

Reports the international readership of the journal and discusses the ways in which the journal, with a primary focus on Scottish literary studies, nonetheless recognizes that Scottish literature is of current political significance and interest

Prelims, Preface to SSL 39: G. Ross Roy and Susan Manning

Preface includes information on usage of the digital version of Studies in Scottish Literature in its first year, together with short tributes to two board members who recently died, the journal\u27s founder G. Ross Roy, and Prof. Susan Manning of the University of Edinburgh

Preface to SSL 43:2

Introduces the two special sections in this issue, on Scottish fiction and Burns bibliography, and briefly describes the range of other contributions, noting the wide international range of contributors

What are the implications for childhood pneumonia of successfully introducing Hib and pneumococcal vaccines in developing countries?

The authors look to the future and imagine the implications of a successful vaccination campaign againstH. influenzae type b and pneumococcus

Prelims, Prefatory Note to SSL 37, Preface to Robert Burns & Friends

Prefatory note by Patrick Scott and Tony Jarrells, preface by Patrick Scott and Kenneth Simpso

The Malaria-High Blood Pressure Hypothesis.

RATIONALE: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. OBJECTIVE: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. METHODS AND RESULTS: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. CONCLUSIONS: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease