Volume 14 Issue 6, June 2008

Long ignored by pharmaceutical companies and global health agencies alike, 'neglected tropical diseases' devastate people in the poorest parts of the world. But they're finally getting the attention they deserve, reports Apoorva Mandavilli.

Finding the financial means to achieve global health targets poses a huge challenge. Government donations can take years or even decades after formal approval to actually arrive. To overcome this hurdle and quickly raise huge sums for child vaccination programs, the International Finance Facility for Immunisation (IFFIm, pronounced 'if im') raises funds from private investors by offering them bonds backed by government pledges. Alan Gillespie, chairman of the board at IFFIm, interfaces between the source of the funds, the capital markets and the distributor, the Global Alliance for Vaccines and Immunization (The GAVI Alliance). Guided by Gillespie, IFFIm has thus far raised over $1 billion for vaccines, which is already flowing through GAVI into childhood immunization programs. Gillespie, who also serves as chairman of the Ulster Bank Group in Belfast, explains IFFIm's unique funding approach to Genevive Bjorn.

A new layer of gene regulation emerges for the metabolic regulator peroxisome proliferator–activated receptor-δ (PPAR-δ). A team consisting of a Krüppel-like transcription factor and a SUMO protease regulate the expression of PPAR-δ target genes, thereby controlling energy metabolism (pages 656–666).

The energy-regulating hormone leptin affects signals emerging from certain brain regions. New results explore the nature of these signals, finding a central role for phosphoinositide-3 kinase in the brain and the endocannabinoid system in adipocytes (pages 667–675).

Clearance of platelets by the liver can help counteract the dangerous blood coagulation that can occur during sepsis. The mechanism involves clearance of platelets through the liver's Ashwell receptor, which binds to platelet glycoproteins altered by sepsis-causing bacteria (pages 648–655).

In 1974, Gilbert Ashwell and Anatol Morell discovered a receptor in the liver that recognizes particular glycoproteins, dubbed asialoglycoproteins. We asked Ashwell about his discoveries and what he thinks of the study by Grewal et al.¹ in this issue, which suggests that the receptor is involved in regulating sepsis.

Infectious agents can induce inflammatory lung disease akin to asthma and chronic obstructive pulmonary disease. Work in a new mouse model provides mechanistic insight into this process and uncovers a key role for invariant natural killer T cells (pages 633–640).

A variety of immune cell types contribute to disease in individuals with multiple sclerosis, an autoimmune condition of the central nervous system. Thomas Prod'homme and Scott Zamvil comment on the 'Bench to Bedside' approach, examining how recent basic research implicates the antigen-presenting cell in this disease. In our 'Bedside to Bench' column, Hans Link explores how recent clinical trials may bolster a mechanistic role for the B cell.

A variety of immune cell types contribute to disease in individuals with multiple sclerosis, an autoimmune condition of the central nervous system. Thomas Prod'homme and Scott Zamvil comment on the 'Bench to Bedside' approach, examining how recent basic research implicates the antigen-presenting cell in this disease. In our 'Bedside to Bench' column, Hans Link explores how recent clinical trials may bolster a mechanistic role for the B cell.