In This Issue
CHEMISTRY
Alkyl chains contort to fit tight spaces
Byron Purse and Julius Rebek, Jr., report that alkanes will readily pack into a container structure when their internal strains are compensated by an attraction to the inner surfaces of the container. In the free space of solutions, the lowest energy state for unbranched alkyl groups is the fully extended anti conformation. A bend along the alkane chain (gauche conformation) can create steric repulsion between hydrogens and increase the free energy requirements. Purse and Rebek examined a series of alkanes covalently attached to a model receptor as ester groups. They prepared a vase-shaped receptor, an introverted acid cavitand, with cavity dimensions of ≈6 Å between the van der Waals surfaces of opposite walls and between the deepest part of the cavity and the upper rim. The shortest chain that can adopt an anti conformation was found to be the propyl ester. Longer esters coiled in response to the constraints of the host, converting from anti to gauche. Esters longer than nine carbons could not compact any more densely and disrupted the folded conformation of the cavitand. A maximum packing coefficient of 0.6 was calculated for the vase-shaped vessel. — F.A.
Encapsulated decane in an extended conformation.
“Self-fulfilling cavitands: Packing alkyl chains into small spaces” by Byron W. Purse and Julius Rebek, Jr. (see pages 2530–2534)
DEVELOPMENTAL BIOLOGY
Eggs derived from primitive sperm cells
Spermatogonia from adult male fish can develop into eggs when placed into female hatchlings, according to Tomoyuki Okutsu et al. Some fish species can switch sex, either spontaneously or artificially by steroid treatment. Researchers have speculated that spermatogonia contain a population of stem cells similar to primordial germ cells, which can differentiate into either type of gamete (egg and sperm). To investigate this possibility, Okutsu et al. isolated testicular germ cells from adult male rainbow trout and transplanted the cells into the peritoneal cavity of newly hatched trout of both sexes. These cells differentiated into sperm in male recipients and eggs in female recipients. The sperm and eggs derived from testicular germ cells were also able to produce normal offspring. The results demonstrate that fish testicular germ cells contain a population of cells that are highly plastic and capable of developing into either type of adult sex cell depending on the recipient’s sex and∕or environmental conditions. The transplant technique described could be used as a rapid breeding tool for generating domestic fish and animals with desirable genetic traits, the authors suggest. — M.M.
Offspring at 8 months from testicular cell-derived eggs.
“Testicular germ cells can colonize sexually undifferentiated embryonic gonad and produce functional eggs in fish” by Tomoyuki Okutsu, Kensuke Suzuki, Yutaka Takeuchi, Toshio Takeuchi, and Goro Yoshizaki (see pages 2725–2729)
MICROBIOLOGY
Several sublineages of H5N1 avian virus
Honglin Chen et al. report that the avian influenza virus H5N1 is genetically and antigenically more diverse than previously thought. The authors isolated a variety of regionally specific H5N1 sublineages from poultry found across Southeast Asia. How H5N1 has perpetuated and spread across this region has remained unclear. Through ongoing systematic influenza surveillance, Chen et al. frequently found H5N1 in market poultry populations and in migratory birds just prior to their seasonal migration. Genetic analysis showed that distinct sublineages of the virus have become established in different geographical regions. Although the findings show that H5N1 can be transmitted over long distances in migratory birds, transport of infected poultry appears to be the main mechanism of H5N1 spread in Southeast Asia. The research suggests that surveillance of H5N1 should be geographically broader to encompass as many genetic and antigenic variants as possible. Also, the study emphasizes the importance of surveillance of apparently healthy birds because no disease outbreaks were observed in the poultry of the regions studied. The genetic diversity and antigenic drift observed within H5N1 populations also may complicate the development of human vaccines for avian flu. — M.M.
Map of eastern Asia showing areas of influenza surveillance.
“Establishment of multiple sublineages of H5N1 influenza virus in Asia: Implications for pandemic control” by H. Chen, G. J. D. Smith, K. S. Li, J. Wang, X. H. Fan, J. M. Rayner, D. Vijaykrishna, J. X. Zhang, L. J. Zhang, C. T. Guo, C. L. Cheung, K. M. Xu, L. Duan, K. Huang, K. Qin, Y. H. C. Leung, W. L. Wu, H. R. Lu, Y. Chen, N. S. Xia, T. S. P. Naipospos, K. Y. Yuen, S. S. Hassan, S. Bahri, T. D. Nguyen, R. G. Webster, J. S. M. Peiris, and Y. Guan (see pages 2845–2850)
NEUROSCIENCE
The tau of neurotoxicity
Giuseppina Amadoro et al. report that the NMDA receptor (NMDAR), the major type of glutamate receptor found in neurons, is involved in the toxic mechanism of the tau protein. Abnormalities of the tau protein have been linked to neuronal death in Alzheimer’s disease and related neurodegenerative disorders, but no clear mechanism of tau toxicity has been defined. In cultured neurons, Amadoro et al. found that the cell death exhibited by tau-infected neurons resembled necrotic death associated with glutamate toxicity. Treating the cells with NMDAR antagonists protected against cell death, confirming the involvement of this neurotransmitter receptor. Caspase inhibitors, which inhibit apoptotic cell death, did not protect tau-infected cells. The authors further found that calpain, which degrades tau protein into highly toxic fragments, and the ERK∕MAPK pathway are important mediators of tau toxicity. The results provide a cellular mechanism linking tau toxicity to NMDAR activation, which may help in elucidating the mechanisms of and developing therapies for neurodegenerative disorders such as Alzheimer’s disease. — M.M.
Tau overexpression induces NMDAR-dependent neurodegeneration.
“NMDA receptor mediates tau-induced neurotoxicity by calpain and ERK∕MAPK activation” by Giuseppina Amadoro, Maria Teresa Ciotti, Marco Costanzi, Vincenzo Cestari, Pietro Calissano, and Nadia Canu (see pages 2892–2897)
PHYSIOLOGY
Hypoxia upregulates nonmuscle myoglobin
Jane Fraser et al. demonstrate that nonmuscle tissues can up-regulate the oxygen-binding hemoprotein myoglobin in response to low oxygen conditions. Previous research has shown that oxidative skeletal and cardiac myocytes express myoglobin, where it plays a role in the physiological response to chronic hypoxia, and myoglobin subfamily proteins were thought to exist exclusively in muscle tissues. Fraser et al. characterized expressed sequence tags in the genome of the common carp (Cyprinus carpio), which routinely experiences environmental hypoxia in isolated ponds. In addition to identifying hemoglobin and cytoglobin isoforms, the authors found two myoglobin isoforms, one corresponding to the known isoform Myg-1 and a second, previously unidentified isoform, Myg-2, that shares 78% sequence identity with Myg-1. Fish exposed to hypoxic conditions for up to 8 days at either 17°C or 30°C were assessed for changes in transcript expression. Myoglobin transcripts in the heart, kidney, liver, brain, skeletal muscles, and gills were detected, although expression in the brain was unaffected by temperature. Myg-2 was expressed solely in the brain, whereas Myg-1 was expressed in the other tissues. Furthermore, the amount of Myg-1 protein in the liver of 5-day hypoxia-treated carp increased almost 3-fold. — F.A.
Carp brain-specific myoglobin isoform.
“Hypoxia-inducible myoglobin expression in nonmuscle tissues” by Jane Fraser, Luciane Vieira de Mello, Deborah Ward, Huw R. Rees, Daryl R. Williams, Yongchang Fang, Andrew Brass, Andrew Y. Gracey, and Andrew R. Cossins (see pages 2977–2981)
