This Week in PNAS

APPLIED PHYSICAL SCIENCES

Imaging of self-assembled phospholipid tubules

Tilt ordering of chiral phospholipids in self-assembled tubules has been imaged with a liquid-crystal optical amplification system, Yue Zhao et al. report. The authors found that the tubules can have both uniform and modulated tilt states. Chiral phospholipids and other related molecules can self-assemble and form cylindrical tubular structures. Based on the chiral interaction, coupled with molecular tilt, theorists predict uniform and modulated tilt states for the tubules. In the uniform tilt state, the tubule has a constant orientation of the molecular tilt with respect to the equator of the cylinder. In the modulated tilt state, the tubule has a periodic modulated orientation of the molecular tilt winding around the cylinder. Zhao et al. used liquid-crystal optical amplification and a polarizing optical microscope to image the tubules and made separate measurements of the tubules' surface with atomic force microscopy. The authors observed that the tubules organized themselves into the uniform and modulated tilt states. Zhao et al. suggest that understanding molecular tilt orientation is a key step in controlling the size and shape of tubules and designing novel nanoscale structures.

“Liquid-crystal imaging of molecular-tilt ordering in self-assembled lipid tubules” by Yue Zhao, Nidhi Mahajan, Ruibo Lu, and Jiyu Fang (see pages 7438–7442)

ENVIRONMENTAL SCIENCES

Human-induced climate change triggers wildlife behavioral shifts

Terry Root et al. report that plant and animal responses to warmer temperatures can be linked to anthropogenic disturbances like greenhouse gas and aerosol production. The authors tested whether observed phenological traits, such as shifts in time of blooming or migration, were linked to temperature trends generated by the HadCM3 General Circulation Model. The authors considered three forcing scenarios: natural, anthropogenic, and combination of natural and anthropogenic forces. Temperatures generated in the combined scenario represent the closest match to actual 20th century climates. Examining 145 species from Europe, North America, and Asia, Root et al. found statistically significant shifts in traits during the spring. Most shifts were negative, with changes occurring earlier in the year at global, hemispheric, regional, and local scales. Larger shifts (–4.4 days/decade) were seen in species at higher latitudes than in those nearer the equator. The most significant associations occurred between species shifts and temperature trends generated via the HadCM3 General Circulation Model combined scenario, as well as the anthropogenic model. These results suggest “joint attribution,” in which human-generated greenhouse gases and aerosols are likely changing surface-air temperatures at all scales, including regional and local, and in turn inducing detectable changes in wild species.

“Human-modified temperatures induce species changes: Joint attribution” by Terry L. Root, Dena P MacMynowski, Michael D. Mastrandrea, and Stephen H. Schneider (see pages 7465–7469)

CELL BIOLOGY

Integrin stimulates tumor growth through VEGF

According to Sarmishtha De et al., αvβ3 integrin regulates the production of VEGF in tumor cells through a p66 Shc-dependent signaling mechanism. Several integrins modulate the signaling of VEGF, the major angiogenic growth factor, though the mechanisms have remained elusive. De et al. studied the ability of αvβ3 integrin, which is found in a variety of cancers, to form tumors in immunodeficient mice. The authors subcutaneously injected the mice with breast and prostate cancer cell lines expressing αvβ3 integrin or the inactive αvβ3 S752P. Mice with inactive integrin had significantly fewer and smaller tumors than those with the active form. The authors determined that the αvβ3 integrin-expressing tumors had increased angiogenesis and detected an increase in VEGF in these tumors. Anti-VEGF antibody decreased both average tumor size and extent of angiogenesis. De et al. found the adapter protein p66 Shc bound to active β3 and phosphorylated to a 3-fold greater extent in cells expressing active versus inactive integrin. The authors expressed a dominant-negative mutant of p66 Shc in the cancer cell lines and observed a significant reduction in the growth of visible tumors and tumor vascularization in mice injected with the cells.

“VEGF–integrin interplay controls tumor growth and vascularization” by Sarmishtha De, Olga Razorenova, Noel Patrick McCabe, Timothy O'Toole, Jun Qin, and Tatiana V. Byzova (see pages 7589–7594)

MEDICAL SCIENCES

Neuropeptides CRF and UcnII modulate small intestine inflammation

Susanne la Fleur et al. employed site-specific RNA interference to show that corticotropin-releasing factor (CRF) and urocortin II (UcnII) are synthesized locally in the ileum of the rat small intestine, where they regulate inflammation and motility. CRF and urocortins are paracrine-signaling neuropeptides involved in responding to environmental stress and are expressed in the CNS and peripheral tissues. The authors determined that CRF is expressed in rat nerve fibers of the submucosal plexus of the ileum, jejunum, and duodenum. The researchers injected interfering dsRNA for CRF (dsCRF) and UcnII (dsUcnII) into the ileal wall and inhibited the basal expression of CRF and UcnII mRNAs and proteins. dsCRF also prevented the induction of CRF expression in rats treated with bacterial Clostridium difficile toxin A (TxA).

The degree of ileal inflammation, the scientists found, was decreased in only dsCRF-treated animals. Peripheral CRF- and UcnII-related mechanisms are known to contribute to intestinal motility. The authors found that silencing CRF but not UcnII increased the total number of fecal pellets excreted by the rats over 24 hours as measured daily for 4 days after injection.

“Role of peripheral corticotropin-releasing factor and urocortin II in intestinal inflammation and motility in terminal ileum” by Susanne E. la Fleur, Elizabeth C. Wick, Prema S. Idumalla, Eileen F. Grady, and Aditi Bhargava (see pages 7647–7652)

PLANT BIOLOGY

How Arabidopsis adapts to low phosphorus levels

Kenji Miura et al. report that AtSIZ1, a small ubiquitin-like modifier (SUMO) E3 ligase, controls phosphate (Pi) starvation-dependent responses in the plant Arabidopsis. Phosphorus can be difficult for plants to acquire because of its uneven distribution and immobilization in the soil, and plants react to Pi limitation by activating a number of adaptive root responses. Miura et al. generated an Arabidopsis mutant exhibiting a more pronounced Pi starvation root architecture response compared with wild-type seedlings and identified the gene AtSIZ1 as being responsible for the mutant phenotype. AtSIZ1 is orthologous to yeast Siz and human PIAS, which function as SUMO ligases. The authors showed that heat shock increased SUMO conjugation in wild-type but not mutant Arabidopsis. The Pi transporter AtPT2, phosphatase AtPS2, and permease AtPS3 were all found to be negatively regulated by AtSIZ1 in Pi-sufficient conditions, whereas AtIPS1 and AtRNS1 (members of the PHR1 regulon) were positively regulated by AtSIZ1 during the initial stages of Pi limitation. In addition, the authors found that PHR1 is a sumoylation target of AtSIZ1 by an in vitro assay.

“The Arabidopsis SUMO E3 ligase SIZ1 controls phosphate deficiency responses” by Kenji Miura, Ana Rus, Altanbadralt Sharkhuu, Shuji Yokoi, Athikkattuvalasu S. Karthikeyan, Kashchandra G. Raghothama, Dongwon Baek, Yoon Duck Koo, Jing Bo Jin, Ray A. Bressan, Dae-Jin Yun, and Paul M. Hasegawa (see pages 7760–7765)