Vacuum Squeezing of Solids: Macroscopic Quantum States Driven by Light Pulses

Femtosecond laser pulses and coherent two-phonon Raman scattering were used to excite KTaO3 into a squeezed state, nearly periodic in time, in which the variance of the atomic displacements dips below the standard quantum limit for half of a cycle. This nonclassical state involves a continuum of transverse acoustic modes that leads to oscillations in the refractive index associated with the frequency of a van Hove singularity in the phonon density of states.     

Eco1-dependent cohesin acetylation during establishment of sister chromatid cohesion

Replicated chromosomes are held together by the chromosomal cohesin complex from the time of their synthesis in S phase onward. This requires the replication fork-associated acetyl transferase Eco1, but Eco1's mechanism of action is not known. We identified spontaneous suppressors of the thermosensitive eco1-1 allele in budding yeast. An acetylation-mimicking mutation of a conserved lysine in cohesin's Smc3 subunit makes Eco1 dispensable for cell growth, and we show that Smc3 is acetylated in an Eco1-dependent manner during DNA replication to promote sister chromatid cohesion. A second set of eco1-1 suppressors inactivate the budding yeast ortholog of the cohesin destabilizer Wapl. Our results indicate that Eco1 modifies cohesin to stabilize sister chromatid cohesion in parallel with a cohesion establishment reaction that is in principle Eco1-independent.     

BRCA2 function in DNA binding and recombination from a BRCA2-DSS1-ssDNA structure

Mutations in the BRCA2 (breast cancer susceptibility gene 2) tumor suppressor lead to chromosomal instability due to defects in the repair of double-strand DNA breaks (DSBs) by homologous recombination, but BRCA2's role in this process has been unclear. Here, we present the 3.1 angstrom crystal structure of a approximately 90-kilodalton BRCA2 domain bound to DSS1, which reveals three oligonucleotide-binding (OB) folds and a helix-turn-helix (HTH) motif. We also (i) demonstrate that this BRCA2 domain binds single-stranded DNA, (ii) present its 3.5 angstrom structure bound to oligo(dT)9, (iii) provide data that implicate the HTH motif in dsDNA binding, and (iv) show that BRCA2 stimulates RAD51-mediated recombination in vitro. These findings establish that BRCA2 functions directly in homologous recombination and provide a structural and biochemical basis for understanding the loss of recombination-mediated DSB repair in BRCA2-associated cancers.     

Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia

Understanding cancer pathogenesis requires knowledge of not only the specific contributory genetic mutations but also the cellular framework in which they arise and function. Here we explore the clonal evolution of a form of childhood precursor-B cell acute lymphoblastic leukemia that is characterized by a chromosomal translocation generating a TEL-AML1 fusion gene. We identify a cell compartment in leukemic children that can propagate leukemia when transplanted in mice. By studying a monochorionic twin pair, one preleukemic and one with frank leukemia, we establish the lineal relationship between these "cancer-propagating" cells and the preleukemic cell in which the TEL-AML1 fusion first arises or has functional impact. Analysis of TEL-AML1-transduced cord blood cells suggests that TEL-AML1 functions as a first-hit mutation by endowing this preleukemic cell with altered self-renewal and survival properties.     

Pattern in escalations in insurgent and terrorist activity

In military planning, it is important to be able to estimate not only the number of fatalities but how often attacks that result in fatalities will take place. We uncovered a simple dynamical pattern that may be used to estimate the escalation rate and timing of fatal attacks. The time difference between fatal attacks by insurgent groups within individual provinces in both Afghanistan and Iraq, and by terrorist groups operating worldwide, gives a potent indicator of the later pace of lethal activity.     

A high-resolution paleoclimate record spanning the past 25,000 years in southern East Africa

High-resolution profiles of the mass accumulation rate of biogenic silica and other geochemical proxies in two piston cores from northern Lake Malawi provide a climate signal for this part of tropical Africa spanning the past 25,000 years. The biogenic silica mass accumulation rate was low during the relatively dry late Pleistocene, when the river flux of silica to the lake was suppressed. Millennial-scale fluctuations, due to upwelling intensity, in the late Pleistocene climate of the Lake Malawi basin appear to have been closely linked to the Northern Hemisphere climate until 11 thousand years ago. Relatively cold conditions in the Northern Hemisphere coincided with more frequent north winds over the Malawi basin, perhaps resulting from a more southward migration of the Intertropical Convergence Zone.