Collapse of long-range charge order tracked by time-resolved photoemission at high momenta

Intense femtosecond (10(-15)?s) light pulses can be used to transform electronic, magnetic and structural order in condensed-matter systems on timescales of electronic and atomic motion. This technique is particularly useful in the study and in the control of materials whose physical properties are governed by the interactions between multiple degrees of freedom. Time- and angle-resolved photoemission spectroscopy is in this context a direct and comprehensive, energy- and momentum-selective probe of the ultrafast processes that couple to the electronic degrees of freedom. Previously, the capability of such studies to access electron momentum space away from zero momentum was, however, restricted owing to limitations of the available probing photon energy. Here, using femtosecond extreme-ultraviolet pulses delivered by a high-harmonic-generation source, we use time- and angle-resolved photoemission spectroscopy to measure the photoinduced vaporization of a charge-ordered state in the potential excitonic insulator 1T-TiSe(2 )(refs 12, 13). By way of stroboscopic imaging of electronic band dispersions at large momentum, in the vicinity of the edge of the first Brillouin zone, we reveal that the collapse of atomic-scale periodic long-range order happens on a timescale as short as 20?femtoseconds. The surprisingly fast response of the system is assigned to screening by the transient generation of free charge carriers. Similar screening scenarios are likely to be relevant in other photoinduced solid-state transitions and may generally determine the response times. Moreover, as electron states with large momenta govern fundamental electronic properties in condensed matter systems, we anticipate that the experimental advance represented by the present study will be useful to study the ultrafast dynamics and microscopic mechanisms of electronic phenomena in a wide range of materials.     

Irregular tropical glacier retreat over the Holocene epoch driven by progressive warming

The causes and timing of tropical glacier fluctuations during the Holocene epoch (10,000 years ago to present) are poorly understood. Yet constraining their sensitivity to changes in climate is important, as these glaciers are both sensitive indicators of climate change and serve as water reservoirs for highland regions. Studies have so far documented extra-tropical glacier fluctuations, but in the tropics, glacier-climate relationships are insufficiently understood. Here we present a (10)Be chronology for the past 11,000?years (11?kyr), using 57 moraines from the Bolivian Telata glacier (in the Cordillera Real mountain range). This chronology indicates that Telata glacier retreated irregularly. A rapid and strong melting from the maximum extent occurred from 10.8?±?0.9 to 8.5?±?0.4?kyr ago, followed by a slower retreat until the Little Ice Age, about 200 years ago. A dramatic increase in the rate of retreat occurred over the twentieth century. A glacier-climate model indicates that, relative to modern climate, annual mean temperature for the Telata glacier region was -3.3?±?0.8 °C cooler at 11?kyr ago and remained -2.1?±?0.8 °C cooler until the end of the Little Ice Age. We suggest that long-term warming of the eastern tropical Pacific and increased atmospheric temperature in response to enhanced austral summer insolation were the main drivers for the long-term Holocene retreat of glaciers in the southern tropics.     

Mechanisms, principles, and Lorentz's cautious realism

I show that Albert Einstein's distinction between principle and constructive theories was predated by Hendrik A. Lorentz's equivalent distinction between mechanism- and principle-theories. I further argue that Lorentz's views toward realism similarly prefigure what Arthur Fine identified as Einstein's “motivational realism.”     

HDAC2 and TXNL1 distinguish aneuploid from diploid colorectal cancers

DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n?=?19), diploid (n?=?31), and aneuploid (n?=?47) carcinomas. The results suggest that distinct protein expression patterns, affecting TXNL1 and HDAC2, distinguish aneuploid with poor prognosis from diploid colorectal cancers.     

Establishment of intestinal homeostasis during the neonatal period

The intestinal mucosa faces the challenge of regulating the balance between immune tolerance towards commensal bacteria, environmental stimuli and food antigens on the one hand, and induction of efficient immune responses against invading pathogens on the other hand. This regulatory task is of critical importance to prevent inappropriate immune activation that may otherwise lead to chronic inflammation, tissue disruption and organ dysfunction. The most striking example for the efficacy of the adaptive nature of the intestinal mucosa is birth. Whereas the body surfaces are protected from environmental and microbial exposure during fetal life, bacterial colonization and contact with potent immunostimulatory substances start immediately after birth. In the present review, we summarize the current knowledge on the mechanisms underlying the transition of the intestinal mucosa during the neonatal period leading to the establishment of a stable, life-long host–microbial homeostasis. The environmental exposure and microbial colonization during the neonatal period, and also the influence of maternal milk on the immune protection of the mucosa and the role of antimicrobial peptides, are described. We further highlight the molecular mechanisms of innate immune tolerance in neonatal intestinal epithelium. Finally, we link the described immunoregulatory mechanisms to the increased susceptibility to inflammatory and infectious diseases during the neonatal period.     

Recombination rates in admixed individuals identified by ancestry-based inference

Studies of recombination and how it varies depend crucially on accurate recombination maps. We propose a new approach for constructing high-resolution maps of relative recombination rates based on the observation of ancestry switch points among admixed individuals. We show the utility of this approach using simulations and by applying it to SNP genotype data from a sample of 2,565 African Americans and 299 African Caribbeans and detecting several hundred thousand recombination events. Comparison of the inferred map with high-resolution maps from non-admixed populations provides evidence of fine-scale differentiation in recombination rates between populations. Overall, the admixed map is well predicted by the average proportion of admixture and the recombination rate estimates from the source populations. The exceptions to this are in areas surrounding known large chromosomal structural variants, specifically inversions. These results suggest that outside of structurally variable regions, admixture does not substantially disrupt the factors controlling recombination rates in humans.     

A genome-wide association study identifies alleles in FGFR2 associated with risk of sporadic postmenopausal breast cancer

We conducted a genome-wide association study (GWAS) of breast cancer by genotyping 528,173 SNPs in 1,145 postmenopausal women of European ancestry with invasive breast cancer and 1,142 controls. We identified four SNPs in intron 2 of FGFR2 (which encodes a receptor tyrosine kinase and is amplified or overexpressed in some breast cancers) that were highly associated with breast cancer and confirmed this association in 1,776 affected individuals and 2,072 controls from three additional studies. Across the four studies, the association with all four SNPs was highly statistically significant (P(trend) for the most strongly associated SNP (rs1219648) = 1.1 x 10(-10); population attributable risk = 16%). Four SNPs at other loci most strongly associated with breast cancer in the initial GWAS were not associated in the replication studies. Our summary results from the GWAS are available online in a form that should speed the identification of additional risk loci.     

Cystatin C modulates cerebral beta-amyloidosis

The CST3 Thr25 allele of CST3, which encodes cystatin C, leads to reduced cystatin C secretion and conveys susceptibility to Alzheimer's disease. Here we show that overexpression of human cystatin C in brains of APP-transgenic mice reduces cerebral amyloid-beta deposition and that cystatin C binds amyloid-beta and inhibits its fibril formation. Our results suggest that cystatin C concentrations modulate cerebral amyloidosis risk and provide an opportunity for genetic risk assessment and therapeutic interventions.