In This Issue
APPLIED PHYSICAL SCIENCES
A density minimum in supercooled water
Unlike most liquids, water reaches a density maximum before it cools to its freezing point. A network of hydrogen bonds connects eachwater molecule to four others and counteracts the contraction caused by loss of thermal energy. Density minima in liquids are even more rare than maxima, but Dazhi Liu et al. report that the density of water reaches a minimum at −63°C. Bulk water, even under high pressure, nucleates and crystallizes well before this point, but the authors were able to maintain water in the liquid state by confining it to porous silica. They measured the density directly by small-angle neutron scattering. The authors found it necessary to use heavy water, D2O, to obtain a sufficiently strong neutron signal, but the nuclear properties do not affect the molecular behavior. The results agree with the density minimum predicted by molecular dynamics modeling. The discovery of the minimum has two major implications when combined with other experimental observations: first, below the minimum, the structure of water approaches a defect-free hydrogen-bond network; second, the results are consistent with existence of a liquid–liquid phase transition and the associated critical point in supercooled water. — K.M.
SANS intensity distribution of supercooled, confined water.
“Observation of the density minimum in deeply supercooled confined water” by Dazhi Liu, Yang Zhang, Chia-Cheng Chen, Chung-Yuan Mou, Peter H. Poole, and Sow-Hsin Chen (see pages 9570–9574)
DEVELOPMENTAL BIOLOGY
Hotei mutation dysregulates sexual development in medaka
In sexual differentiation studies, medaka, a small freshwater ricefish nativeto east and southeastern Asia, including Japan, makes an ideal model organism. The fish's sex is primarily genetically determined through the XX/XY chromosome system, which is analogous to the mammalian system. Chikako Morinaga et al. discovered that a mutation in the anti-Müllerian hormone receptor type II (amhrII) gene causes the dysregulation of germ cell and sexual development in medaka. The authors observed amhrII expression in the somatic cells of the gonads of both sexes of the fish. The mutation, called hotei (hot), manifested itself in a number of ways: regardless of sex, the fish overproduced germ cells; meiosis in male hot homozygotes initiated prematurely; half of hot homozygous XY fish switched their sex; and phenotypically female homozygotes prematurely terminated follicular development. An amhrII transgene rescued these abnormalities. The authors say that the varied phenotypes of hot homozygotes indicate that there are multiple regulatory functions of the anti-Müllerian hormone/anti-Müllerian hormone receptor signaling system in gonadal development. — F.A.
Female medaka with hotei mutation has a large, oocyte-filled abdomen.
“The hotei mutation of medaka in the anti-Müllerian hormone receptor causes the dysregulation of germ cell and sexual development” by Chikako Morinaga, Daisuke Saito, Shuhei Nakamura, Takashi Sasaki, Shuichi Asakawa, Nobuyoshi Shimizu, Hiroshi Mitani, Makoto Furutani-Seiki, Minoru Tanaka, and Hisato Kondoh (see pages 9691–9696)
EVOLUTION
Marsupial sex chromosome silencing
The Y sex chromosome contains much less genetic information than the X. However, mammalian sex genes are expressed at the same levels in males (XY) and females (XX) because one of the X-chromosomes is silenced in females. The details of X silencing in eutherians, one of three mammal subclades along with marsupials and monotremes, are well known: itis regulated by a group of genes in the “X-inactivation center” (XIC). However, an XIC analog has not been found in marsupials. Satoshi Namekawa et al. report a study in opossum, a marsupial, in which they find that the X-chromosome is silenced by the paternal germ line. This form of germ-line-driven silencing may explain imprinted paternal X-inactivation in the female embryo. The authors extracted meiotic cells from opossum testicles and identified inactive DNA with a DAPI stain as well as fluorescence in situ hybridization. The fluorescence images revealed that the X-chromosome shuts down RNA transcription early in prophase. Epigenetic modifications such as histone trimethylation account for the silencing. The mechanism is similar to that seen in eutherians, which suggests that imprinting has conserved the phenomenon in the absence of the XIC genes. — K.M.
Pachytene spermatocytes in the male germ line of the South American opossum.
“Sex chromosome silencing in the marsupial male germ line” by Satoshi H. Namekawa, John L. VandeBerg, John R. McCarrey, and Jeannie T. Lee (see pages 9730–9735)
GENETICS
Prions form with the help of lipids and polyanions
In prion diseases such as bovine spongiform encephalopathy (BSE), Creutzfeldt–Jakob disease (CJD), and scrapie, conformationalchanges in the wild-type host PrPc protein that transform it into the infectious, disease-associated PrPSc form play a critical role in pathogenesis. However, this conversion mechanism is not well understood. Using the protein misfolding cyclic amplification (PMCA) technique, Nathan Deleault et al. found that this transformation could be provoked by incubating purified PrPc with only copurified lipids and a synthetic, single-stranded RNA polyanion. PMCA multiplies misfolded prions as PCR amplifies DNA, and the technique usually requires an abnormal seed protein like PrPSc as catalyst. Inoculation of the PMCA-derived PrPSc proteins into hamsters caused scrapie, which could be transmitted to other animals on second passage. The authors' results limit the possible composition of infectious prions, and suggest that endogenous lipids and polyanions may help catalyze the conformational changes that lead to prion formation in sporadic forms of prion disease such as human CJD. — F.A.
Hippocampus with abundant spongiform degeneration.
“Formation of native prions from minimal components in vitro” by Nathan R. Deleault, Brent T. Harris, Judy R. Rees, and Surachai Supattapone (see pages 9741–9746)
NEUROSCIENCE
Purkinje cell abnormalities in fetal alcohol syndrome
Fetal alcohol syndrome (FAS) is the leading cause of mental retardation in Western countries. One symptom of FAS is dysfunctionin fine motor skills, which many researchers believe is due to reduced numbers of cerebellar Purkinje cells. Laurent Servais et al. report that even surviving Purkinje cells are abnormal in mice with FAS. The authors observed clumsiness and altered motor learning in young FAS mice. Synapses between parallel fibers and Purkinje cells had been converted from long-term depression, in which a burst of repeated stimulation induces a weaker response in the Purkinje cell over an extended period, to long-term potentiation, in which the Purkinje cell responds more strongly to input. Long-term depression is thought to be central in motor learning, and altered calcium entry is known to cause the shift from long-term depression to potentiation. The authors examined voltage-gated calcium currents, which were weakened in the Purkinje cells, and also detected reduced expression of membrane-bound protein kinase C, a key element in voltage-gated calcium channel activation. Addition of protein kinase C activator restored normal calcium entry. These results may help direct further research toward therapy for FAS. — K.M.
A normal Purkinje cell of the cerebellar cortex.
“Purkinje cell dysfunction and alteration of long-term synaptic plasticity in fetal alcohol syndrome” by Laurent Servais, Raphaël Hourez, Bertrand Bearzatto, David Gall, Serge N. Schiffmann, and Guy Cheron (see pages 9858–9863)
