The XPF-ERCC1 endonuclease and homologous recombination contribute to the repair of minor groove DNA interstrand crosslinks inmammalian cells produced by the pyrrolo[2,1-c][1,4]benzodiazepine dimer SJG-136

SJG-136, a pyrrolo[2,1-c][1,4]benzodiazepine (PBD) dimer, is a highly efficient interstrand crosslinking agent that reacts with guanine bases in a 5'-GATC-3' sequence in the DNA minor groove. SJG-136 crosslinks form rapidly and persist compared to those produced by conventional crosslinking agents such as nitrogen mustard, melphalan or cisplatin which bind in the DNA major groove. A panel of Chinese hamster ovary (CHO) cells with defined defects in specific DNA repair pathways were exposed to the bi-functional agents SJG-136 and melphalan, and to their mono-functional analogues mmy-SJG and mono-functional melphalan. SJG-136 was >100 times more cytotoxic than melphalan, and the bi-functional agents were much more cytotoxic than their respective mono-functional analogues. Cellular sensitivity of both SJG-136 and melphalan was dependent on the XPF-ERCC1 heterodimer, and homologous recombination repair factors XRCC2 and XRCC3. The relative level of sensitivity of these repair mutant cell lines to SJG-136 was, however, significantly less than with major groove crosslinking agents. In contrast to melphalan, there was no clear correlation between sensitivity to SJG-136 and crosslink unhooking capacity measured using a modified comet assay. Furthermore, repair of SJG-136 crosslinks did not involve the formation of DNA double-strand breaks. SJG-136 cytotoxicity is likely to result from the poor recognition of DNA damage by repair proteins resulting in the slow repair of both mono-adducts and more importantly crosslinks in the minor groove

Are silica defences in grasses driving vole population cycles?

Understanding the factors that drive species population dynamics is fundamental to biology. Cyclic populations of microtine rodents have been the most intensively studied to date, yet there remains great uncertainty over the mechanisms determining the dynamics of most of these populations. For one such population, we present preliminary evidence for a novel mechanism by which herbivore-induced reductions in plant quality alter herbivore life-history parameters and subsequent population growth. We tested the effect of high silica levels on the population growth and individual performance of voles (Microtus agrestis) reared on their winter food plant (Deschampsia caespitosa). In sites where the vole population density was high, silica levels in D. caespitosa leaves collected several months later were also high and vole populations subsequently declined; in sites where the vole densities were low, levels of silica were low and population density increased. High silica levels in their food reduced vole body mass by 0.5% a day. We argue that silica-based defences in grasses may play a key role in driving vole population cycles

Effective potential and stability of the rigid membrane

The calculation of the effective potential for fixed-end and toroidal rigid $p$-branes is performed in the one-loop as well as in the $1/d$ approximations. The analysis of the involved zeta-functions (of inhomogeneous Epstein type) which appear in the process of regularization is done in full detail. Assymptotic formulas (allowing only for exponentially decreasing errors of order $\leq 10^{-3}$) are found which carry all the dependences on the basic parameters of the theory explicitly. The behaviour of the effective potential (specified to the membrane case $p=2$) is investigated, and the extrema of this effective potential are obtained.Comment: 15 PAGE

Conformational Free-Energy Landscapes for a Peptide in Saline Environments

AbstractThe conformations that proteins adopt in solution are a function of both their primary structure and surrounding aqueous environment. Recent experimental and computational work on small peptides, e.g., polyK, polyE, and polyR, have highlighted an interesting and unusual behavior in the presence of aqueous ions such as ClO4−, Na+, and K+. Notwithstanding the aforementioned studies, as of this writing, the nature of the driving force induced by the presence of ions and its role on the conformational stability of peptides remains only partially understood. Molecular-dynamics simulations have been performed on the heptapeptide AEAAAEA in NaCl and KCl solutions at concentrations of 0.5, 1.0, and 2.0 M. Metadynamics in conjunction with a three-dimensional model reaction coordinate was used to sample the conformational space of the peptide. All simulations were run for 2 μs. Free-energy landscapes were computed over the model reaction coordinate for the peptide in each saline assay as well as in the absence of ions. Circular dichroism spectra were also calculated from each trajectory. In the presence of Na+ and K+ ions, no increase in helicity is observed with respect to the conformation in pure water

Some discussions on functionalist housing and its economics in Romania by Lhe late 1950s and early 1960s

This paper proposes an analysis of the Romanian architectural practices in the late 1950's and early 1960's by considering the availability of financial resources. I premise that echoes of Moscow's approaches to the built environment overlapped the Bucharest politicians' priorities, whose lack of constancy in economic decision-making exacerbated itself as the urban construction programs advanced. From the Romanian authorities' point of view, therefore, raising the mass housing profitability could save important financial resources for other investments in heavy industry, while maintaining the appearance of a social state. Similarities between Soviet and Romanian modernist building projects suggested a coherent approach to housing throughout the bloc. However, this article will show that functionalist architectural modernism -cheap and fast to erect- also proved beneficial for Gheorghe Gheorghiu-Dej's economic plans, which questions urban construction projects' political agendas and the professional tensions between architects and economists. Therefore, investigating the functionalist architecture opens up several lines of inquiry: to what extent Nikita Khrushchev's housing program was transferred in Romania; the tortuous policies of the Romanian state's leadership in the field of housing as well as how local bureaucratic or professional actors appropriated, interpreted and adjusted such programs; and, the economic costs of the new functionalist approach to urban dwelling. In this way, this article reads the making of functionalist mass housing programs by the late 1950s to assess the Soviets' part in building the Romanian cities. To this end, the article contributes to the recent scholarly literature on multiple modernities

Atmosphere, ecology and evolution: what drove the Miocene expansion of C4 grasslands?

Grasses using the C4 photosynthetic pathway dominate today's savanna ecosystems and account for ∼20% of terrestrial carbon fixation. However, this dominant status was reached only recently, during a period of C4 grassland expansion in the Late Miocene and Early Pliocene (4–8 Myr ago). Declining atmospheric CO2 has long been considered the key driver of this event, but new geological evidence casts doubt on the idea, forcing a reconsideration of the environmental cues for C4 plant success.Here, I evaluate the current hypotheses and debate in this field, beginning with a discussion of the role of CO2 in the evolutionary origins, rather than expansion, of C4 grasses. Atmospheric CO2 starvation is a plausible selection agent for the C4 pathway, but a time gap of around 10 Myr remains between major decreases in CO2 during the Oligocene, and the earliest current evidence of C4 plants.An emerging ecological perspective explains the Miocene expansion of C4 grasslands via changes in climatic seasonality and the occurrence of fire. However, the climatic drivers of this event are debated and may vary among geographical regions.Uncertainty in these areas could be reduced significantly by new directions in ecological research, especially the discovery that grass species richness along rainfall gradients shows contrasting patterns in different C4 clades. By re-evaluating a published data set, I show that increasing seasonality of rainfall is linked to changes in the relative abundance of the major C4 grass clades Paniceae and Andropogoneae. I propose that the explicit inclusion of these ecological patterns would significantly strengthen climate change hypotheses of Miocene C4 grassland expansion. Critically, they allow a new series of testable predictions to be made about the fossil record.Synthesis. This paper offers a novel framework for integrating modern ecological patterns into theories about the geological history of C4 plants

Pre-M Phase-promoting Factor Associates with Annulate Lamellae in Xenopus Oocytes and Egg Extracts

We have used complementary biochemical and in vivo approaches to study the compartmentalization of M phase-promoting factor (MPF) in prophase Xenopus eggs and oocytes. We first examined the distribution of MPF (Cdc2/CyclinB2) and membranous organelles in high-speed extracts of Xenopus eggs made during mitotic prophase. These extracts were found to lack mitochondria, Golgi membranes, and most endoplasmic reticulum (ER) but to contain the bulk of the pre-MPF pool. This pre-MPF could be pelleted by further centrifugation along with components necessary to activate it. On activation, Cdc2/CyclinB2 moved into the soluble fraction. Electron microscopy and Western blot analysis showed that the pre-MPF pellet contained a specific ER subdomain comprising "annulate lamellae" (AL): stacked ER membranes highly enriched in nuclear pores. Colocalization of pre-MPF with AL was demonstrated by anti-CyclinB2 immunofluorescence in prophase oocytes, in which AL are positioned close to the vegetal surface. Green fluorescent protein-CyclinB2 expressed in oocytes also localized at AL. These data suggest that inactive MPF associates with nuclear envelope components just before activation. This association may explain why nuclei and centrosomes stimulate MPF activation and provide a mechanism for targeting of MPF to some of its key substrates

An ALMA Survey of the SCUBA-2 Cosmology Legacy Survey UKIDSS/UDS Field: Number Counts of Submillimeter Galaxies

We report the first results of AS2UDS, an 870 μm continuum survey with the Atacama Large Millimeter/Submillimeter Array (ALMA) of a total area of ~50 arcmin2 comprising a complete sample of 716 submillimeter sources drawn from the SCUBA-2 Cosmology Legacy Survey (S2CLS) map of the UKIDSS/UDS field. The S2CLS parent sample covers a 0.96 degree2 field at σ 850 = 0.90 ± 0.05 mJy beam−1. Our deep, high-resolution ALMA observations with σ 870 ~ 0.25 mJy and a 0farcs15–0farcs30 FWHM synthesized beam, provide precise locations for 695 submillimeter galaxies (SMGs) responsible for the submillimeter emission corresponding to 606 sources in the low-resolution, single-dish map. We measure the number counts of SMGs brighter than S 870 ≥ 4 mJy, free from the effects of blending and show that the normalization of the counts falls by 28% ± 2% in comparison with the SCUBA-2 published counts, but that the shape remains unchanged. We determine that ${44}_{-14}^{+16}$% of the brighter single-dish sources with S 850 ≥ 9 mJy consist of a blend of two or more ALMA-detectable SMGs brighter than S 870 ~ 1 mJy (corresponding to a galaxy with a total-infrared luminosity of L IR gsim 1012 L ⊙), in comparison with 28% ± 2% for the single-dish sources at S 850 ≥ 5 mJy. Using the 46 single-dish submillimeter sources that contain two or more ALMA-detected SMGs with photometric redshifts, we show that there is a significant statistical excess of pairs of SMGs with similar redshifts (<1% probability of occurring by chance), suggesting that at least 30% of these blends arise from physically associated pairs of SMGs

Recovery of release cloud from laser shock-loaded graphite and hydrocarbon targets: in search of diamonds

This work presents first insights into the dynamics of free-surface release clouds from dynamically compressed polystyrene and pyrolytic graphite at pressures up to 200 GPa, where they transform into diamond or lonsdaleite, respectively. These ejecta clouds are released into either vacuum or various types of catcher systems, and are monitored with high-speed recordings (frame rates up to 10 MHz). Molecular dynamics simulations are used to give insights to the rate of diamond preservation throughout the free expansion and the catcher impact process, highlighting the challenges of diamond retrieval. Raman spectroscopy data show graphitic signatures on a catcher plate confirming that the shock-compressed PS is transformed. First electron microscopy analyses of solid catcher plates yield an outstanding number of different spherical-like objects in the size range between ten(s) up to hundreds of nanometres, which are one type of two potential diamond candidates identified. The origin of some objects can unambiguously be assigned, while the history of others remains speculative

The VANDELS ESO public spectroscopic survey

VANDELS is a uniquely deep spectroscopic survey of high-redshift galaxies with the VIMOS spectrograph on ESO’s Very Large Telescope (VLT). The survey has obtained ultradeep optical (0.48 < λ < 1.0 μ m) spectroscopy of ≃2100 galaxies within the redshift interval 1.0 ≤ z ≤ 7.0, over a total area of ≃0.2 deg2 centred on the CANDELS Ultra Deep Survey and Chandra Deep Field South fields. Based on accurate photometric redshift pre-selection, 85 per cent of the galaxies targeted by VANDELS were selected to be at z ≥ 3. Exploiting the red sensitivity of the refurbished VIMOS spectrograph, the fundamental aim of the survey is to provide the high-signal-to-noise ratio spectra necessary to measure key physical properties such as stellar population ages, masses, metallicities, and outflow velocities from detailed absorption-line studies. Using integration times calculated to produce an approximately constant signal-to-noise ratio (20 < tint< 80 h), the VANDELS survey targeted: (a) bright star-forming galaxies at 2.4 ≤ z ≤ 5.5, (b) massive quiescent galaxies at 1.0 ≤ z ≤ 2.5, (c) fainter star-forming galaxies at 3.0 ≤ z ≤ 7.0, and (d) X-ray/Spitzer-selected active galactic nuclei and Herschel-detected galaxies. By targeting two extragalactic survey fields with superb multiwavelength imaging data, VANDELS will produce a unique legacy data set for exploring the physics underpinning high-redshift galaxy evolution. In this paper, we provide an overview of the VANDELS survey designed to support the science exploitation of the first ESO public data release, focusing on the scientific motivation, survey design, and target selection