Inhibition of DDAH1, but not DDAH2, results in apoptosis of a human trophoblast cell line in response to TRAIL.

STUDY QUESTION: Does inhibition of dimethylarginine dimethylaminohydrolase (DDAH) increase the sensitivity of trophoblasts to TRAIL-induced apoptosis? SUMMARY ANSWER: Inhibition of DDAH1, but not DDAH2, increases the sensitivity of trophoblasts to TRAIL-induced apoptosis. WHAT IS KNOWN ALREADY: Successful human pregnancy is dependent on adequate trophoblast invasion and remodelling of the maternal spiral arteries. Increased trophoblast apoptosis is seen in pregnancies complicated by pre-eclampsia. The mechanism underlying this increase is unknown. We have previously shown that nitric oxide (NO) is involved in regulating trophoblast motility and invasion, and have also demonstrated an important role for NO in regulating trophoblast sensitivity to apoptotic stimuli. DDAH is an enzyme that metabolizes asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis, previously shown to be elevated in the plasma of pre-eclamptic mothers. STUDY DESIGN, SIZE, DURATION: This study used the human extravillous trophoblast-derived cell line SGHPL-4 cells. All experiments were performed at least three times. PARTICIPANTS/MATERIALS, SETTING, METHODS: The effect of DDAH on trophoblast apoptosis was examined using siRNA and time-lapse microscopy. Changes in the expression of DDAH were followed by PCR and western blot analysis. Receptor expression was followed by flow cytometry. MAIN RESULTS AND THE ROLE OF CHANCE: Inhibiting the expression of DDAH1, but not DDAH2, resulted in a significant increase in the sensitivity of the EVT cell line SGHPL-4 to tumour necrosis factor related apoptosis inducing ligand (TRAIL) induced apoptosis (P < 0.01). This response could be mimicked by the addition of Asymmetric Dimethylarginine (ADMA), an endogenous inhibitor of NO synthesis and the substrate for both isoforms of DDAH. We further showed that this increased sensitivity to apoptosis is accompanied by a significant increase in the expression of TRAIL receptor 2 (TR2; P < 0.05) but not TRAIL receptor 1 (TR1). LIMITATIONS, REASONS FOR CAUTION: This study was performed only in vitro using a well characterized trophoblast cell line, SGHPL-4, derived from first trimester extravillous trophoblasts. WIDER IMPLICATIONS OF THE FINDINGS: This study provides new insight into the role of the DDAH/ADMA pathway in the regulation of trophoblast function. Both dysregulation of DDAH and the accumulation of ADMA have been associated with the development of pre-eclampsia. This is the first study to implicate the DDAH/ADMA pathway as a mechanism that might underlie the poor trophoblast invasion seen in this common pregnancy disorder. STUDY FUNDING/COMPETING INTERESTS: B.A.L. was supported by a grant from Action Medical Research UK (SP4577). A.E.W. was supported by a grant from the Wellcome Trust (091550). There are no competing interests and the authors have no conflict interest to declare

Star formation and AGN feedback in the local universe: combining radio continuum and integral field spectroscopy

Galaxie

Cladoceran birth and death rates estimates

I. Birth and death rates of natural cladoceran populations cannot be measured directly. Estimates of these population parameters must be calculated using methods that make assumptions about the form of population growth. These methods generally assume that the population has a stable age distribution. 2. To assess the effect of variable age distributions, we tested six egg ratio methods for estimating birth and death rates with data from thirty-seven laboratory populations of Daphnia pulicaria. The populations were grown under constant conditions, but the initial age distributions and egg ratios of the populations varied. Actual death rates were virtually zero, so the difference between the estimated and actual death rates measured the error in both birth and death rate estimates. 3. The results demonstrate that unstable population structures may produce large errors in the birth and death rates estimated by any of these methods. Among the methods tested, Taylor and Slatkin's formula and Paloheimo's formula were most reliable for the experimental data. 4. Further analyses of three of the methods were made using computer simulations of growth of age-structured populations with initially unstable age distributions. These analyses show that the time interval between sampling strongly influences the reliability of birth and death rate estimates. At a sampling interval of 2.5 days (equal to the duration of the egg stage), Paloheimo's formula was most accurate. At longer intervals (7.5–10 days), Taylor and Slatkin's formula which includes information on population structure was most accurate

Geology of the Abu Dhabi 1:100 000 map sheet, 100-16, United Arab Emirates

This Sheet Description describes the Quaternary and solid geology of the Abu Dhabi 1:100 000 scale geological map. The Abu Dhabi district covers 3620 km2 along the Arabian Gulf coast including the northern part of Saadiyat island, Abu Dhabi, part of the Mussafah district and many of the islands to the west. These include Futaisi, Bu Kesheishah, Halat al Bharaini, Al Dabiya, Bu Qumah, Bu Shara, Al Qanatir and Al Rafiq. The sheet also includes a significant part of the coastal plain southwest of Abu Dhabi between Shunayyin in the east to Borquat al Rashid in the west, and south to Maharqah, across which the main E11 coastal highway runs. In the southeast of the district, an area of higher ground is formed of Miocene rocks draped by a variable sequence of cemented and unconsolidated dune sand. The region hosts several major oilfields including the Rumaitha, Shanayel, Al Dabb’iya, Umm al Dalkh, Al Mutarib and Umm al Lulu fields. The region is dominated by a series of offshore islands, part of a chain of barrier islands that extend from north of Abu Dhabi to Marawah Island, west of the present area. These islands, along with the sea-ward margin of the coastal plain are mostly comprised of a thin sequence of intensively studied Holocene marine carbonates termed the Abu Dhabi Formation. These sediments represent a transgressive-regressive sequence, and form the classic carbonate-evaporitic ‘sabkhas’ for which the region is justly famous. The Abu Dhabi Formation includes a range of marine and supratidal facies including coastal spits, bars and beach ridges, lagoonal muds, algal mats and ooidal tidal deltas deposited over the last 10 000 years. The southern limit of the Holocene transgression is marked by a beach ridge running parallel to the coast and clearly visible on satellite imagery. The barrier islands commonly have a core of well-cemented Pleistocene carbonate dune sand (Ghayathi Formation) around which the carbonate spits, bars and ridges of the Abu Dhabi Formation were accreted. The islands have been largely deflated down to the local water-table leading to the development of extensive sabkhas. Consequently, the islands are generally flat but punctuated by small Ghayathi Formation mesas and zeugen, forming mushroom-shaped outcrops rising up to 6 m above sea-level, locally capped with marine limestones of the Late Pleistocene Fuwayrit Formation. Offshore to the north of the island, below low water, is the Great Pearl Bank, an area of reefs and coralgal sands named after the former pearling industry in the region. South of the Holocene beach ridge, much of the onshore area is an extensive, very gently sloping coastal plain, dominated by a deflated planation surface developed on either unconsolidated quartzose aeolian sand or well cemented carbonate grainstones of the Ghayathi Formation. The deflation surface is commonly marked by secondary gypsum forming a sabkha. The Ghayathi Formation palaeodunes are locally well exposed, forming spectacular wind-sculpted mesas and zeugen both on the islands and within the lagoons, but also onshore draping the Miocene rocks in the southeast of the district

Euler-Poincar\'e approaches to nematodynamics

Nematodynamics is the orientation dynamics of flowless liquid-crystals. We show how Euler-Poincar\'e reduction produces a unifying framework for various theories, including Ericksen-Leslie, Luhiller-Rey, and Eringen's micropolar theory. In particular, we show that these theories are all compatible with each other and some of them allow for more general configurations involving a non vanishing discination density. All results are also extended to flowing liquid crystals.Comment: 26 pages, no figure

The Williams Scale of Attitude toward Paganism: development and application among British Pagans

This article builds on the tradition of attitudinal measures of religiosity established by Leslie Francis and colleagues with the Francis Scale of Attitude toward Christianity (and reflected in the Sahin-Francis Scale of Attitude toward Islam, the Katz-Francis Scale of Attitude toward Judaism, and the Santosh-Francis Scale of Attitude toward Hinduism) by introducing a new measure to assess the attitudinal disposition of Pagans. A battery of items was completed by 75 members of a Pagan Summer Camp. These items were reduced to produce a 21-item scale that measured aspects of Paganism concerned with: the God/Goddess, worshipping, prayer, and coven. The scale recorded an alpha coefficient of 0.93. Construct validity of the Williams Scale of Attitude toward Paganism was demonstrated by the clear association with measures of participation in private rituals

Star formation and AGN feedback in the local Universe: combining LOFAR and MaNGA

Galaxie

Search for the standard model Higgs boson decaying into two photons in pp collisions at sqrt(s)=7 TeV

A search for a Higgs boson decaying into two photons is described. The analysis is performed using a dataset recorded by the CMS experiment at the LHC from pp collisions at a centre-of-mass energy of 7 TeV, which corresponds to an integrated luminosity of 4.8 inverse femtobarns. Limits are set on the cross section of the standard model Higgs boson decaying to two photons. The expected exclusion limit at 95% confidence level is between 1.4 and 2.4 times the standard model cross section in the mass range between 110 and 150 GeV. The analysis of the data excludes, at 95% confidence level, the standard model Higgs boson decaying into two photons in the mass range 128 to 132 GeV. The largest excess of events above the expected standard model background is observed for a Higgs boson mass hypothesis of 124 GeV with a local significance of 3.1 sigma. The global significance of observing an excess with a local significance greater than 3.1 sigma anywhere in the search range 110-150 GeV is estimated to be 1.8 sigma. More data are required to ascertain the origin of this excess.Comment: Submitted to Physics Letters

Search for a W' boson decaying to a bottom quark and a top quark in pp collisions at sqrt(s) = 7 TeV

Results are presented from a search for a W' boson using a dataset corresponding to 5.0 inverse femtobarns of integrated luminosity collected during 2011 by the CMS experiment at the LHC in pp collisions at sqrt(s)=7 TeV. The W' boson is modeled as a heavy W boson, but different scenarios for the couplings to fermions are considered, involving both left-handed and right-handed chiral projections of the fermions, as well as an arbitrary mixture of the two. The search is performed in the decay channel W' to t b, leading to a final state signature with a single lepton (e, mu), missing transverse energy, and jets, at least one of which is tagged as a b-jet. A W' boson that couples to fermions with the same coupling constant as the W, but to the right-handed rather than left-handed chiral projections, is excluded for masses below 1.85 TeV at the 95% confidence level. For the first time using LHC data, constraints on the W' gauge coupling for a set of left- and right-handed coupling combinations have been placed. These results represent a significant improvement over previously published limits.Comment: Submitted to Physics Letters B. Replaced with version publishe

Measurement of isolated photon production in pp and PbPb collisions at sqrt(sNN) = 2.76 TeV

Isolated photon production is measured in proton-proton and lead-lead collisions at nucleon-nucleon centre-of-mass energies of 2.76 TeV in the pseudorapidity range |eta|<1.44 and transverse energies ET between 20 and 80 GeV with the CMS detector at the LHC. The measured ET spectra are found to be in good agreement with next-to-leading-order perturbative QCD predictions. The ratio of PbPb to pp isolated photon ET-differential yields, scaled by the number of incoherent nucleon-nucleon collisions, is consistent with unity for all PbPb reaction centralities.Comment: Submitted to Physics Letters