bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract PR3: The BLM helicase facilitates RNA polymerase l-mediated ribosomal RNA transcription
Authors: Grierson Patrick , Lillard Kate , Behbehani Gregory , Combs Kelly , Bhattacharyya Saumitri , Samir Acharya , Groden Joanna 
Published: June 2012

Abstract
Bloom's syndrome (BS) is an autosomal recessive disorder that is invariably characterized by cancer predisposition and idiopathic growth retardation. The BLM helicase, mutations of which lead to BS, localizes to the nucleolus of the cell, the site of RNA polymerase l-mediated ribosomal RNA (rRNA) transcription. rRNA transcription is fundamental for ribosome biogenesis and therefore protein synthesis, cellular growth and proliferation; its inhibition limits cellular growth and proliferation as well as bodily growth. Disorders with defective ribosome biogenesis, such as Diamond-Blackfan anemia and Shwachman-Diamond syndrome, display similar cancer predisposition and growth abnormalities to BS. The objective of this study was to investigate a potential mechanism underlying the proportional dwarfism of BS. We tested the hypothesis that the BLM helicase facilitates rRNA transcription as a component of an RNA polymerase I-associated complex, which when deficient has the potential to lead to proportional dwarfism. We report that nucleolar BLM facilitates RNA polymerase I-mediated rRNA transcription using H3-uridine pulse-chase assays and nuclear run-on assays in cells with an innate or experimentally induced BLM deficiency. In vitro helicase assays demonstrate that BLM unwinds GC-rich hybrid RNA/DNA nucleic acid substrates predicted to form in the nucleolus during rRNA transcription; the persistence of such structures inhibits progression of the RNA polymerase I transcription complex. Immunofluorescence studies using actinomycin D at a concentration that inhibits RNA polymerase I demonstrate the dependence of BLM nucleolar localization upon ongoing RNA polymerase l-mediated rRNA transcription. Finally, in vivo protein co-immunoprecipitation shows that BLM physically associates with RNA polymerase I in the nucleolus. These studies suggest that nucleolar BLM interacts with RNA polymerase I and facilitates rRNA transcription by modulating rDNA structure. Given the intricate relationship between rDNA metabolism and growth, our data may help to understand the etiology of the proportional dwarfism in Bloom's syndrome. Furthermore, this work provides greater understanding of the mechanisms regulating rRNA transcription and ribosome biogenesis, processes currently being exploited in cancer therapeutics.
This abstract is also presented as Poster B34.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr PR3.
Abstract PR-04: Physical activity and risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC): Results for different tumor subtypes
Authors: Steindorf Karen 
Published: June 2012

Abstract
Physical activity has been identified as protective factor for invasive breast cancer risk in several studies, whereas studies on in situ carcinoma are rare. Studies investigating whether this association is valid for all breast cancer subtypes defined by the estrogen receptor (ER) and the progesterone receptor (PR) status yielded inconsistent results.
Material and methods: The study is based on data from 283,680 female participants from the multinational EPIC-cohort study, for whom detailed information on recreational household and occupational physical activity as well as smoking habits, dietary habits, anthropometry and socio-demographic variables were assessed at the baseline examination between 1992 and 2000. Adjusted hazard ratios (HR) were estimated by proportional hazards models. For outcome variables with more than 2 levels competing risk models were applied. During a median follow-up period of 11.7 years, 9,947 incident breast cancer cases were identified, including 1,060 carcinoma in situ. Out of the 8,887 invasive breast cancer cases the estrogen receptor status, the progesterone receptor status and the combined status of the tumor could be assessed for 6,007 (67.6%), 4,814 (54.2%), and 4798 (53.9%) cases, respectively.
Results: For invasive tumors, breast cancer risk was inversely associated with high levels of total physical activity (HR=0.85, 95% confidence interval (CI): 0.77–0.93, p-trend&lt;0.001) and of recreational activity (HR=0.88, 95%-CI: 0.82–0.94, p&lt;0.001), comparing the highest to the lowest activity quartile. Effects for postmenopausal breast cancer (HR=0.81, 95%-CI: 0.70–0.93, p=0.002 for total physical activity, HR=0.89, 95%-CI: 0.81–0.97, p=0.005 for recreational activity) were slightly stronger than for premenopausal breast (HR=0.87, 95%-KI: 0.72–1.04, p=0.082 for total physical activity, HR=0.84, 95%-KI 0.72–0.98, p=0.032 recreational activity). The analyses by hormone receptor status indicated differential effects with stronger effects of total physical activity for hormone receptor positive (ER+/PR+) breast tumors, compared to the other combinations (p-value for test of heterogeneity: p=0.043). More detailed analyses showed that primarily the PR status (p-heterogeneity: 0.006) rather than the ER status (p-heterogeneity 0.235) dominated this result. For in situ carcinoma no associations for any of the physical activity variables were found.
Conclusions: The protective effects for physical activity on breast cancer risk could be confirmed. The results of this largest prospective study on physical activity and different hormone receptor status indicate that physical activity primarily reduces the risk for PR+ and ER+/PR+ tumors. The result strengthens the hypothesis that the reduction of breast cancer risk by physical activity is at least partly related to hormonal pathways.
Citation Information: Cancer Prev Res 2011;4(10 Suppl):PR-04.
Microphysical Structure of the Marine Boundary Layer under Strong Wind and Spray Formation as Seen from Simulations Using a 2D Explicit Microphysical Model. Part II: The Role of Sea Spray
Authors: Shpund J. , Zhang J. A. , Pinsky M. , Khain A. 
Published: June 2012

AbstractThe effect of sea spray on the thermodynamics and microphysical structure of the lowest 400-m layer under strong wind speeds is investigated using a 2D hybrid Lagrangian–Eulerian model with spectral bin microphysics. A large number of adjacent and interacting Lagrangian parcels move within a turbulent-like flow with the largest vortices being interpreted as large eddies (LE) with characteristic velocity of a few meters per second.It is shown that sea spray effect strongly depends on the environmental conditions, and largely on relative humidity (RH). When RH &lt; ~90%, spray evaporates and contributes to moistening and cooling of the boundary layer, as well as to an increase in surface fluxes. When RH &gt; ~90% the effects of spray on the BL thermodynamics substantially decrease. Spray leads to formation of drizzle by collisions with droplets formed on background aerosols.It is also shown that LE transport about 20% of large spray drops with radius exceeding 150 μm to the upper levels of the atmospheric mixed layer. It is hypothesized that this effect is of much importance with regard to the spray effect on the microphysics and dynamics of deep convective clouds typical of a hurricane eyewall.
Mean Biases, Variability, and Trends in Air–Sea Fluxes and Sea Surface Temperature in the CCSM4
Authors: Bates Susan C. , Fox-Kemper Baylor , Jayne Steven R. , Large William G. , Stevenson Samantha , Yeager Stephen G. 
Published: June 2012

Abstract
Air–sea fluxes from the Community Climate System Model version 4 (CCSM4) are compared with the Coordinated Ocean-Ice Reference Experiment (CORE) dataset to assess present-day mean biases, variability errors, and late twentieth-century trend differences. CCSM4 is improved over the previous version, CCSM3, in both air–sea heat and freshwater fluxes in some regions; however, a large increase in net shortwave radiation into the ocean may contribute to an enhanced hydrological cycle. The authors provide a new baseline for assessment of flux variance at annual and interannual frequency bands in future model versions and contribute a new metric for assessing the coupling between the atmospheric and oceanic planetary boundary layer (PBL) schemes of any climate model. Maps of the ratio of CCSM4 variance to CORE reveal that variance on annual time scales has larger error than on interannual time scales and that different processes cause errors in mean, annual, and interannual frequency bands. Air temperature and specific humidity in the CCSM4 atmospheric boundary layer (ABL) follow the sea surface conditions much more closely than is found in CORE. Sensible and latent heat fluxes are less of a negative feedback to sea surface temperature warming in the CCSM4 than in the CORE data with the model’s PBL allowing for more heating of the ocean’s surface.
Variations in Tropical Cyclone Genesis Factors in Simulations of the Holocene Epoch
Authors: Korty Robert L. , Camargo Suzana J. , Galewsky Joseph 
Published: June 2012

Abstract
The thermodynamic factors related to tropical cyclone genesis are examined in several simulations of the middle part of the Holocene epoch when the precession of Earth’s orbit altered the seasonal distribution of solar radiation and in one transient simulation of the millennium preceding the industrial era. The thermodynamic properties most crucial for genesis display a broad stability across both periods, although both orbital variations during the mid-Holocene (MH) 6000 years ago (6ka) and volcanic eruptions in the transient simulation have detectable effects. It is shown that the distribution of top-of-the-atmosphere radiation 6ka altered the Northern Hemisphere seasonal cycle of the potential intensity of tropical cyclones in addition to slightly increasing the difference between middle tropospheric and boundary layer entropy, a parameter that has been related to the incubation period required for genesis. The Southern Hemisphere, which receives more solar radiation during its storm season today than it did 6ka, displays slightly more favorable thermodynamic properties during the MH than in the preindustrial era control. Surface temperatures over the ocean in both hemispheres respond to radiation anomalies more slowly than those in upper levels, altering the thermal stability.
Volcanism produces a sharp but transient temperature response in the last-millennium simulation that strongly reduces potential intensity during the seasons immediately following a major eruption. Here, too, the differential vertical temperature response is key: temperatures in the lower and middle troposphere cool, while those near the tropopause rise. Aside from these deviations, there is no substantial variation in thermodynamic properties over the 1000-yr simulation.
Effects of Diurnal Cycle on a Simulated Asian Summer Monsoon
Authors: Hong Song-You , Kanamitsu Masao , Kim Jung-Eun , Koo Myung-Seo 
Published: June 2012

AbstractThis study investigates the effects of the diurnal cycle on monsoonal circulations over Asia in summer with a focus on precipitation. To this end, two sets of experiments are designed in a regional climate modeling framework forced by reanalysis data. The control experiment is a normal integration in which radiation is computed hourly, whereas the no-diurnal experiment is an experimental integration in which the daily averaged solar flux is computed once a day. Analysis of the results from the two experiments reveals that the diurnal cycle enhances the daily averaged sensible heat flux over land and the latent flux over oceans, which means that daytime net solar heating exceeds nighttime cooling in terms of the effects in surface climate and monsoonal circulations. Seasonal precipitation increased by about 3% over land and 11% over oceans. The surface hydroclimate over land is strongly influenced by the interaction between land and the atmosphere, and results in cooler surface temperatures except over the Tibetan Plateau. Over oceans, a robust increase in precipitation results from enhanced planetary boundary layer mixing. The diurnal cycle over the Tibetan Plateau region is found to decrease surface albedo by melting snow during the daytime, which contributes to the formation of the thermal low near the surface and the Tibetan high in the upper troposphere. The resultant monsoonal precipitation is modulated by an increase (decrease) in precipitation over northern (southern) India. This modulation results in the summer monsoon over East Asia being shifted northward.
Evidence for Enhanced Land–Atmosphere Feedback in a Warming Climate
Authors: Dirmeyer Paul A. , Cash Benjamin A. , Kinter James L. , Stan Cristiana , Jung Thomas , Marx Lawrence , Towers Peter , Wedi Nils , Adams Jennifer M. , Altshuler Eric L. , Huang Bohua , Jin Emilia K. , Manganello Julia 
Published: June 2012

Abstract
Global simulations have been conducted with the European Centre for Medium-Range Weather Forecasts operational model run at T1279 resolution for multiple decades representing climate from the late twentieth and late twenty-first centuries. Changes in key components of the water cycle are examined, focusing on variations at short time scales. Metrics of coupling and feedbacks between soil moisture and surface fluxes and between surface fluxes and properties of the planetary boundary layer (PBL) are inspected. Features of precipitation and other water cycle trends from coupled climate model consensus projections are well simulated. Extreme 6-hourly rainfall totals become more intense over much of the globe, suggesting an increased risk for flash floods. Seasonal-scale droughts are projected to escalate over much of the subtropics and midlatitudes during summer, while tropical and winter droughts become less likely. These changes are accompanied by an increase in the responsiveness of surface evapotranspiration to soil moisture variations. Even though daytime PBL depths increase over most locations in the next century, greater latent heat fluxes also occur over most land areas, contributing a larger energy effect per unit mass of air, except over some semiarid regions. This general increase in land–atmosphere coupling is represented in a combined metric as a “land coupling index” that incorporates the terrestrial and atmospheric effects together. The enhanced feedbacks are consistent with the precipitation changes, but a causal connection cannot be made without further sensitivity studies. Nevertheless, this approach could be applied to the output of traditional climate change simulations to assess changes in land–atmosphere feedbacks.
A Process-Oriented Small Lake Scheme for Coupled Climate Modeling Applications
Authors: MacKay Murray D. 
Published: June 2012

Abstract
A one-dimensional dynamic lake model is presented as a candidate for simulating small unresolved lakes within the land surface scheme of a regional or global climate model. This model is based largely on well-established process algorithms with some exceptions. The complete nonlinear surface energy balance is computed in a skin layer of arbitrary thickness in order to ensure rapid response times with the atmosphere. Turbulent mixing in the surface mixed layer is achieved through stirring and buoyancy production as well as shear production along the diurnal thermocline. The net effect of Kelvin–Helmholtz instability on thermocline structure is grossly accounted for by computing a linear temperature profile within a thermocline layer. The energetics of billowing is not considered; however, a significant thermocline leakage term is included. The model has been incorporated into the Canadian Land Surface Scheme and used to estimate regional turbulent sensible and latent heat fluxes over the Experimental Lakes Area in the boreal forest of northwestern Ontario—an area about 30% lake covered. It is demonstrated that the presence of open water has a significant effect on the net flux exchange with the atmosphere in this region. Sensible heat flux to the atmosphere is suppressed during the summer stratified period but enhanced in the fall, resulting in an increased accumulation of about 5% by the end of the open water season due to the presence of lakes. Turbulent latent heat flux to the atmosphere is more enhanced during autumn, with a final accumulation about 24% larger.
The Unpredictable Nature of Internal Tides on Continental Shelves
Authors: Nash Jonathan D. , Kelly Samuel M. , Shroyer Emily L. , Moum James N. , Duda Timothy F. 
Published: June 2012

Abstract
Packets of nonlinear internal waves (NLIWs) in a small area of the Mid-Atlantic Bight were 10 times more energetic during a local neap tide than during the preceding spring tide. This counterintuitive result cannot be explained if the waves are generated near the shelf break by the local barotropic tide since changes in shelfbreak stratification explain only a small fraction of the variability in barotropic to baroclinic conversion. Instead, this study suggests that the occurrence of strong NLIWs was caused by the shoaling of distantly generated internal tides with amplitudes that are uncorrelated with the local spring-neap cycle. An extensive set of moored observations show that NLIWs are correlated with the internal tide but uncorrelated with barotropic tide. Using harmonic analysis of a 40-day record, this study associates steady-phase motions at the shelf break with waves generated by the local barotropic tide and variable-phase motions with the shoaling of distantly generated internal tides. The dual sources of internal tide energy (local or remote) mean that shelf internal tides and NLIWs will be predictable with a local model only if the locally generated internal tides are significantly stronger than shoaling internal tides. Since the depth-integrated internal tide energy in the open ocean can greatly exceed that on the shelf, it is likely that shoaling internal tides control the energetics on shelves that are directly exposed to the open ocean.
Humans accumulate microsatellite instability with acquired loss of MLH1 protein in hematopoietic stem and progenitor cells as a function of age
Authors: Kenyon Jonathan , Fu Pingfu , Lingas Karen , Thomas Emily , Saurastri Anshul , Santos Guasch Gabriela , Wald David , Gerson Stanton L. 
Published: June 2012

AbstractHematopoietic stem and progenitor cells (HPCs) are necessary for long-term survival. Genomic instability and persistent DNA damage may cause loss of adult stem cell function. The mismatch repair (MMR) pathway increases replication fidelity and defects have been implicated in malignant hematopoietic diseases. Little, however, is known about the role MMR pathway failure plays in the aging process of human HPCs. We hypothesized that loss of MMR occurs in HPCs as a process of human aging. We examined microsatellite instability and expression of the MMR genes MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in HPCs and colony-forming cell-derived clones (CFCs) from human donors aged 0 to 86 years. CFCs from donors > 45 years had a greater frequency of microsatellite instability and CD34+ progenitors lacking MLH1 expression and protein than individuals ≤ 45 years. Loss of MSH2 did not correlate with age. Thus, a potentially early event in the normal human aging process is microsatellite instability accumulation in normal human HPCs associated with the loss of MLH1 protein expression.
EGNAS: an exhaustive DNA sequence design algorithm
Authors: Kick Alfred , Bönsch Martin , Mertig Michael 
Published: June 2012

AbstractBackgroundThe molecular recognition based on the complementary base pairing of deoxyribonucleic acid (DNA) is the fundamental principle in the fields of genetics, DNA nanotechnology and DNA computing. We present an exhaustive DNA sequence design algorithm that allows to generate sets containing a maximum number of sequences with defined properties. EGNAS (Exhaustive Generation of Nucleic Acid Sequences) offers the possibility of controlling both interstrand and intrastrand properties. The guanine-cytosine content can be adjusted. Sequences can be forced to start and end with guanine or cytosine. This option reduces the risk of “fraying” of DNA strands. It is possible to limit cross hybridizations of a defined length, and to adjust the uniqueness of sequences. Self-complementarity and hairpin structures of certain length can be avoided. Sequences and subsequences can optionally be forbidden. Furthermore, sequences can be designed to have minimum interactions with predefined strands and neighboring sequences.ResultsThe algorithm is realized in a C++ program. TAG sequences can be generated and combined with primers for single-base extension reactions, which were described for multiplexed genotyping of single nucleotide polymorphisms. Thereby, possible foldback through intrastrand interaction of TAG-primer pairs can be limited. The design of sequences for specific attachment of molecular constructs to DNA origami is presented.ConclusionsWe developed a new software tool called EGNAS for the design of unique nucleic acid sequences. The presented exhaustive algorithm allows to generate greater sets of sequences than with previous software and equal constraints. EGNAS is freely available for noncommercial use athttp://www.chm.tu-dresden.de/pc6/EGNAS.
Potential role for PADI-mediated histone citrullination in preimplantation development
Authors: Kan Rui , Jin Mei , Subramanian Venkataraman , Causey Corey P , Thompson Paul R , Coonrod Scott A 
Published: June 2012

Abstract

Background
The peptidylarginine deiminases (PADIs) convert positively charged arginine residues to neutrally charged citrulline on protein substrates in a process that is known as citrullination or deimination. Previous reports have documented roles for histone citrullination in chromatin remodeling and gene regulation in several tissue types, however, a potential role for histone citrullination in chromatin-based activities during early embryogenesis has not been investigated.

Results
In the present study, we tested by laser scanning confocal indirect immunofluorescence microscopy whether specific arginine residues on the histone H3 and H4 N-terminal tails (H4R3, H3R2 + 8 + 17, and H3R26) were citrullinated in mouse oocytes and preimplantation embryos. Results showed that all of the tested residues were deiminated with each site showing a unique localization pattern during early development. Given these findings, we next tested whether inhibition of PADI activity using the PADI-specific inhibitor, Cl-amidine, may affect embryonic development. We found that treatment of pronuclear stage zygotes with Cl-amidine reduces both histone H3 and H4 tail citrullination and also potently blocks early cleavage divisions in vitro. Additionally, we found that the Cl-amidine treatment reduces acetylation at histone H3K9, H3K18, and H4K5 while having no apparent effect on the repressive histone H3K9 dimethylation modification. Lastly, we found that treatment of zygotes with trichostatin A (TSA) to induce hyperacetylation also resulted in an increase in histone citrullination at H3R2 + 8 + 17.

Conclusions
Given the observed effects of Cl-amidine on embryonic development and the well documented correlation between histone acetylation and transcriptional activation, our findings suggest that histone citrullination may play an important role in facilitating gene expression in early embryos by creating a chromatin environment that is permissive for histone acetylation.