Reviews & Analysis

Findings in mice suggest that treatment with VEGF inhibitors prompts the upregulation of erythropoietin (Epo), a powerful cytokine and regulator of blood cell development. Could Epo be dulling the therapeutic effects of VEGF inhibition?

Animal models of schizophrenia are incomplete, and human brain tissue has been difficult to study. Results from postmortem human tissue begin to overcome these hurdles and find a role for modulation of NMDA type glutamate receptors (pages 824–828).

A metagenomic analysis of the microbes in the human gut reveals their diversity and just how interdependent we are on them. Together with our microbes we are a human-bacterial superorganism with immense metabolic diversity and capacity.

Two studies examine the microbe-fighting peptides that keep infection at bay in the urinary tract and the colon. In the urinary tract, such peptides are deployed with lightning speed, and in the colon a short-chain fatty acid induces the peptides and fends off dysentery caused by Shigella species (pages 636 – 641).

Massive numbers of T cells infiltrate the epithelial cells of the intestine in people with celiac disease, caused by hypersensitivity to gluten. New findings show how some of these T cells become dangerous by taking on the characteristics of natural killer cells.

The multitasking signaling protein mTOR integrates nutritional and hormonal cues in the brain, modulating feeding and body weight.

For years, clinicians have administered antibodies and other protein-based drugs intravenously. Findings in mice suggest that, for at least one such agent, a pill might also work (pages 627–635).

Osteoclasts carve out the marrow space where hematopoietic stem cells reside, but they have been considered bystanders during hematopoiesis. Osteoclasts are now shown to mediate stem cell mobilization, enabling stem cell emigration from the marrow to the circulation (pages 657 – 664).

Marijuana receptors are present in fibrogenic cells of the liver, and their expression is induced in cirrhosis. Blockade of the CB₁ subtype is now shown to inhibit fibrogenesis, offering a new approach for the treatment of cirrhosis (pages 671 – 676).

The central position of estrogen in the physiological and pharmacological control of bone resorption is now challenged by evidence from mouse genetics of estrogen-independent control by pituitary FSH.

Being in constant contact with the environment, the lung has evolved special mechanisms for resisting infections such as influenza. A newly discovered mechanism assures that influenza-specific T cells do not enter the general circulation. Instead, they recirculate between the draining lymph node and the respiratory mucosa—so remaining close to the site of infection.

Multiple sclerosis occurs when T cells attack myelin in the central nervous system. Experiments in a mouse model of the disease suggest that neurons fight back by inducing regulatory T cells that dampen the immune response (pages 518–525).

A new approach to killing tumors combines two methods that each alone have shortcomings. A tumor-killing virus is loaded into a cell type that homes to tumors, thereby evading the antiviral immune response.

Ciliary neurotrophic factor (CNTF) enhances fatty-acid oxidation in muscle and reduces insulin resistance in obese, diabetic mice. Because skeletal muscle is the major site of insulin-mediated glucose uptake, this action of CNTF could benefit individuals with diabetes (pages 541–548).

The versatile neurotransmitter GABA acquires a new role in the control of appetite by the hypothalamus. In this region of the brain, a regulator of GABA_A receptor expression seems to respond to energy levels (pages 526–533).

In vitro experiments have suggested that the TRPA1 ion channel senses various noxious stimuli. Many of these findings are now borne out in mice, in line with the notion that TRPA1 inhbitors might be useful in treating pain.