The Walter Reed Project, Kisumu Field Station: Impact of Research on Malaria Policy, Management, and Prevention.

The Walter Reed Project is a collaboration between the Walter Reed Army Institute of Research of the United States Department of Defense and the Kenya Medical Research Institute. The Kisumu field station, comprising four campuses, has until recently been devoted primarily to research on malaria countermeasures. The Kombewa Clinical Research Center is dedicated to conducting regulated clinical trials of therapeutic and vaccine candidates in development.

Deployment of Rotavirus Vaccine in Western Kenya Coincides with a Reduction in All-Cause Child Mortality: A Retrospective Cohort Study.

Rotavirus is an important cause of fatal pediatric diarrhea worldwide. Many national immunization programs began adding rotavirus vaccine following a 2009 World Health Organization recommendation. Kenya added rotavirus vaccine to their immunization program at the end of 2014.

Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial.

Background: Emergence of drug resistance demands novel antimalarial drugs with new mechanisms of action. We aimed to identify effective and well tolerated doses of ganaplacide plus lumefantrine solid dispersion formulation (SDF) in patients with uncomplicated Plasmodium falciparum malaria.

Methods: This open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial was conducted at 13 research clinics and general hospitals in ten African and Asian countries.

RNA Therapeutics in Cardiovascular Disease.

Noncoding RNAs have been shown to exert important physiological and pathophysiological functions. Various studies suggest that modulating noncoding RNAs may provide a therapeutic option. Noncoding RNAs comprise small RNAs, mainly microRNAs, and long noncoding RNAs.

Myeloid Kdm6b deficiency results in advanced atherosclerosis.

Background And Aims: Atherosclerosis is a lipid-driven chronic inflammatory disorder of the arteries, and monocytes and macrophages play a central role in this process. Within the atherosclerotic lesion, macrophages can scavenge modified lipids and become the so-called foam cells. We previously reported that the epigenetic enzyme Kdm6b (also known as Jmjd3) controls the pro-fibrotic transcriptional profile of peritoneal foam cells.

Host-mediated selection impacts the diversity of Plasmodium falciparum antigens within infections.

Host immunity exerts strong selective pressure on pathogens. Population-level genetic analysis can identify signatures of this selection, but these signatures reflect the net selective effect of all hosts and vectors in a population. In contrast, analysis of pathogen diversity within hosts provides information on individual, host-specific selection pressures.

Clonal Expansion of Endothelial Cells Contributes to Ischemia-Induced Neovascularization.

Rationale: Vascularization is critical to maintain organ function. Although many molecular pathways were shown to control vessel growth, the genuine process of capillary formation under different conditions is unclear.

Objective: Here, we elucidated whether clonal expansion contributes to vessel growth by using Confetti mice for genetic tracing of clonally expanding endothelial cells (ECs).

Light-inducible antimiR-92a as a therapeutic strategy to promote skin repair in healing-impaired diabetic mice.

MicroRNAs (miRs) are small non-coding RNAs that post-transcriptionally control gene expression. Inhibition of miRs by antisense RNAs (antimiRs) might be a therapeutic option for many diseases, but systemic inhibition can have adverse effects. Here we show that light-activatable antimiRs efficiently and locally restricted target miR activity in vivo.

Shear stress-regulated miR-27b controls pericyte recruitment by repressing SEMA6A and SEMA6D.

Aims: Vessel maturation involves the recruitment of mural cells such as pericytes and smooth muscle cells. Laminar shear stress is a major trigger for vessel maturation, but the molecular mechanisms by which shear stress affects recruitment of pericytes are unclear. MicroRNAs (miRs) are small non-coding RNAs, which post-transcriptionally control gene expression.

Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells.

Aim: In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells.

Materials & Methods: Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis.

Results: Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells.

JMJD8 Regulates Angiogenic Sprouting and Cellular Metabolism by Interacting With Pyruvate Kinase M2 in Endothelial Cells.

Objective: Jumonji C (JmjC) domain-containing proteins modify histone and nonhistone proteins thereby controlling cellular functions. However, the role of JmjC proteins in angiogenesis is largely unknown. Here, we characterize the expression of JmjC domain-containing proteins after inducing endothelial differentiation of murine embryonic stem cells and study the function of JmjC domain-only proteins in endothelial cell (EC) functions.

Distinct functions of epidermal and myeloid-derived VEGF-A in skin tumorigenesis mediated by HPV8.

Beta human papillomaviruses (HPV) have been suspected to be carcinogenic in nonmelanoma skin cancers (NMSC), but the basis for potential viral contributions to these cancers is poorly understood. In particular, it is unresolved how HPV-infected keratinocytes escape cell-cycle control and whether their cross-talk with immune cells is critical for tumorigenesis. In nonviral preclinical models, the angiogenic cytokine VEGF-A has been identified as a critical regulator of NMSC.

Laminar shear stress inhibits endothelial cell metabolism via KLF2-mediated repression of PFKFB3.

Objective: Cellular metabolism was recently shown to regulate endothelial cell phenotype profoundly. Whether the atheroprotective biomechanical stimulus elicited by laminar shear stress modulates endothelial cell metabolism is not known.

Approach And Results: Here, we show that laminar flow exposure reduced glucose uptake and mitochondrial content in endothelium.

CCR2 recruits an inflammatory macrophage subpopulation critical for angiogenesis in tissue repair.

Monocytes/macrophages are critical in orchestrating the tissue-repair response. However, the mechanisms that govern macrophage regenerative activities during the sequential phases of repair are largely unknown. In the present study, we examined the dynamics and functions of diverse monocyte/macrophage phenotypes during the sequential stages of skin repair.

Differential roles of macrophages in diverse phases of skin repair.

Influx of macrophages plays a crucial role in tissue repair. However, the precise function of macrophages during the healing response has remained a subject of debate due to their functional dichotomy as effectors of both tissue injury and repair. We tested the hypothesis that macrophages recruited during the diverse phases of skin repair after mechanical injury exert specific functions to restore tissue integrity.

Simultaneous fitting of real-time PCR data with efficiency of amplification modeled as Gaussian function of target fluorescence.

Background: In real-time PCR, it is necessary to consider the efficiency of amplification (EA) of amplicons in order to determine initial target levels properly. EAs can be deduced from standard curves, but these involve extra effort and cost and may yield invalid EAs. Alternatively, EA can be extracted from individual fluorescence curves.