Volume 20 Issue 7, July 2014

Last month, Martin Stratmann began a six-year term as president of the Munich-based Max Planck Society. Stratmann spoke with David Levine about his vision for the society and about what the change of guard will mean for biomedical research.

The only vaccine ever approved to protect against Lyme disease was pulled off the market in 2002, and drugmakers have yet to offer an alternative. What's taking so long? Cassandra Willyard investigates.

Diamond-Blackfan anemia (DBA) is an inherited hypoplastic anemia characterized by impaired production of erythroid cells, and it is caused by inactivating mutations in ribosomal protein genes in more than half of all cases. A new study in human cells demonstrates that reduced translation of the transcription factor GATA1, as a consequence of ribosomal protein haploinsufficiency, is a crucial factor in mediating the erythroid defect found in DBA (pages 748–753).

Leptin deficiency, which is associated with type 1 diabetes, is a critical factor in the pathophysiology of this disease, a new study in rats shows. The lack of this hormone triggers a cascade of neuroendocrine events that affect adipose tissue and the liver, resulting in hyperglycemia and ketoacidosis (pages 759–763).

Stress has long been thought to be a major contributing factor to cardiovascular disease, although little is known about the underlying cellular mechanisms. A new study in humans and mice suggests that chronic stress promotes hematopoietic stem cell proliferation in bone marrow, leading to increased leukocyte production, circulation and recruitment to the vasculature (pages 754–758).

Oxidative stress has long been linked to disease development and accelerated aging, prompting professionals in the biomedical field to suggest the use of antioxidants to prevent or even reverse these conditions. But growing clinical evidence is showing that this in fact might not be effective, calling for additional investigation to prove that certain molecular factors involved in oxidation, specifically reactive oxidative species (ROS), are not detrimental. In “Bedside to Bench,” Michael Ristow highlights recent human studies with antioxidant supplementation that have failed to show any improvement in health span. Moreover, other relevant evidence has pointed towards a beneficial role for ROS in lifespan under stress conditions, although how this is mediated and regulated inside the cell is not fully understood. In “Bench to Bedside,” Hiroyuki Kawagishi and Toren Finkel peruse the biological and signaling underpinnings of ROS in living organisms, which suggest different amounts of ROS may explain their dual role in lifespan and disease and the lack of effect of antioxidants in the body. The authors propose targeting pathways and molecules involved in removing cellular damage rather than ROS, which could make therapies to increase lifespan more effective and preclude diseases caused by oxidation and aging.

Mounia Tannour-Louet and her colleagues show that 1–3% of cases of male genitourinary tract malformations are associated with increased copy number variations of the VAMP7 gene, which encodes a SNARE protein involved in vesicular transport. They show that overexpression of human VAMP7 in mice is sufficient to replicate the condition in this species and that the phenotype is due to alterations in the balance between androgen and estrogen signaling.

Neisseria meningitidis is the causative agent of potentially fatal meningitis and septic shock, induced by bacterial colonization of blood vessels in the brain and the periphery. The endothelial cell receptor mediating meningococcal adhesion to blood vessels has previously been unknown. Here Sandrine Bourdoulous and colleagues report that CD147 expressed on human endothelial cells is a crucial mediator of N. meningitidis vascular colonization, providing new insight into some of the mechanisms that give rise to meningococcal disease.

Cancers dependent on hedgehog pathway signaling are susceptible to the BET bromodomain inhibitor JQ1.

The antiangiogenic and profibrinolytic activities of the N-terminal fragment of prolactin, 16K PRL, are mediated by its binding to the protein PAI-1.

Ribosomal protein deficiency in Diamond-Blackfan anemia impairs protein translation of the key erythroid transcription factor GATA1.

Activation of bone marrow hematopoietic stem cells by chronic stress raises circulating leukocyte levels and increases atherosclerotic plaque inflammation.

Treatment with exogenous leptin has been reported to improve hyperglycemia in mouse models of type 1 diabetes through lowering of glucagon signaling. Jerry Shulman and his colleagues now report that the more primary beneficial effect of leptin on hyperglycemia is by reducing the activity of the hypothalamic-pituitary-adrenal axis. These results give further credence to the possible use of leptin therapy for this form of diabetes.

Gustavo Turecki and colleagues report that miR-1202, a miRNA specific to primates, is decreased in individuals with depression and seems to be differentially regulated in individuals who will end up showing beneficial responses to antidepressant treatment compared to those who will not respond.

Modeling and documenting malignant progression in vitro without the need for in vivo transplantation represents a clear step forward for cancer investigation. Using an air-liquid interface methodology, Xingnan Li and colleagues show they can robustly model a range of gastrointestinal malignancies from pancreas, stomach and colon in primary epithelial/mesenchymal organoid culture. This setup is able to generate detailed histologic endpoints for oncogenic transformation in vitro and demonstrate in vivo tumorigenicity when the organoids are transplanted.

Multidrug and radiation resistance, as well as nonspecific toxic effects of some drugs, currently limit some cancer therapies. Ekaterina Lukianova-Hleb and colleagues address this with the development of an intracellular drug release system using plasmonic nanobubbles for the on-demand release of the encapsulated payload from nanocarriers, achieving high target cell specificity and intracellular concentration and enhanced therapeutic efficacy of both drugs and X-rays. Validation is shown in aggressive and multidrug resistant head and neck squamous cell carcinoma using encapsulated doxorubicin and paclitaxel.

Repetitive dynamic two-photon imaging of retinoid cycle fluorophores and subcellular details of their location within the retinal pigment epithelium in intact eyes of live mice.

Tim Berendsen and colleagues describe an approach for long-term liver preservation based on cryopreservation, supercooling and machine perfusion where rat livers preserved for 4 d remain viable following transplantation.