Reviews & Analysis

Manipulation of cell renewal pathways creates T memory stem cells that can generate a sustained and targeted immune response. These findings have broad implications for vaccine development and immunotherapy (pages 808–813).

To maintain skeletal integrity and prevent fractures, degradation and rebuilding of bone must occur in synchrony. Transforming growth factor-β1 is now found to coordinate this restructuring process: the molecule is released during bone degradation and stimulates bone rebuilding (pages 757–765).

Two receptors have now been identified for the virus behind severe hand, foot and mouth disease (pages 794–797 and 798–801).

A monoclonal antibody directed against lymphotoxin-α (LT-α) expressed by pathogenic T cells can prompt the clearance of these cells from the body (pages 766–773). The findings bring us one step closer to targeting only the cell populations that cause harm in autoimmune diseases while leaving beneficial arms of the immune system largely intact.

Platelets accumulate on the downstream face of a developing blood clot after local changes in blood flow. These findings offer new insights into how platelets pile up at sites of vascular injury (pages 665–673).

Calcium deficiency in the elderly is associated with low gastric acid secretion and bone loss. A new study linking defects in gastric acid secretion with bone destruction and impaired mineralization bolsters the view that calcium supplements can prevent these bone defects—but do they all work (pages 674–681)?

Blood vessels arise from progenitor cells, grow and branch by sprouting from preexisting vessels and remodel by splitting longitudinally. A new study proposes an additional mechanism. It seems that vascularization can proceed through the mechanical translocation and expansion of existing vessels, which loop into vascularising tissue (pages 657–664).

The cytokine interferon-α stimulates the turnover and proliferation of hematopoietic cells in vivo (pages 696–700). The findings hint at a new strategy to treat hematopoietic cancers.

Studies of schizophrenia have been plagued by shortcomings such as weak genetic association with disease, inadequate animal models and limited replication of gene expression findings. Future success may lie not in overcoming any one of these limitations but in a broad approach strengthening the evidence in each area. Using such an approach, neuroscientists have uncovered a new gene behind the disease (pages 509–518).

After an increase in dietary salt, the excess sodium is stored under the skin—stimulating lymphatic growth through the activity of macrophages (pages 545–552). The findings should recast thinking about how blood pressure is regulated.

Current attempts to block angiogenesis during cancer and other diseases are limited partly by their effects on normal angiogenic processes. Could a more targeted approach emerge from the identification of a factor required for pathological angiogenesis under conditions of hypoxia (pages 553–558)?

The chromosomes of human embryos seem to be more unstable than previously thought. An analysis of embryos derived from in vitro fertilization reveals high rates of structural abnormalities (pages 577–583).

Growth factors used to accelerate engraftment after hematopoietic cell transplantation can increase the severity of graft-versus-host disease. Experiments with mice examine how irradiation, used to prepare recipients for transplants, contributes to this problem (pages 436–441).

Experiments in rodents identify a factor that causes the release of multipotent cells into the circulation after injury. These cells contribute to tissue repair (pages 425–435).

Experiments in two mouse models of thromboinflammatory disease show how neutrophils stick to red blood cells and platelets—leading to reduced blood flow and damage to the microcirculation. Polarized expression of α_Mβ₂ integrins on neutrophils helps set the process in motion (pages 384–391).

Toll-like receptors on lung epithelia recognize allergens and help provoke asthma. The findings put new emphasis on innate immunity as a driver of allergic responses (pages 410–416).

A remote, downstream event in the pathology of muscular dystrophy may have a key role in the disease (pages 325–330). It seems that induction of nitric oxide synthase causes calcium to leak inside the cell through ryanodine receptors. The findings provide new options for therapeutic interventions.

Findings in knockout mice indicate that hypoxia-sensitive pathways modulate the glucose-sensing machinery of pancreatic beta cells. Conditions that mimic hypoxia severely impair glucose-stimulated insulin release.

Three studies implicate Kindlin-3, a molecule that mediates signaling through integrins, in a rare disorder characterized by spontaneous bleeding and susceptibility to infection (pages 300–305, 306–312 and 313–318).