bluuebunny/crossref_metadata_2025 huggingface dataset:
Endothelial TLR4 activation impairs intestinal microcirculatory perfusion in necrotizing enterocolitis via eNOS–NO–nitrite signaling
Authors: Yazji Ibrahim , Sodhi Chhinder P. , Lee Elizabeth K. , Good Misty , Egan Charlotte E. , Afrazi Amin , Neal Matthew D. , Jia Hongpeng , Lin Joyce , Ma Congrong , Branca Maria F. , Prindle Thomas , Richardson Ward M. , Ozolek John , Billiar Timothy R. , Binion David G. , Gladwin Mark T. , Hackam David J.
Published: May 2013

Necrotizing enterocolitis (NEC) is a devastating disease of premature infants characterized by severe intestinal necrosis and for which breast milk represents the most effective protective strategy. Previous studies have revealed a critical role for the lipopolysaccharide receptor toll-like receptor 4 (TLR4) in NEC development through its induction of mucosal injury, yet the reasons for which intestinal ischemia in NEC occurs in the first place remain unknown. We hypothesize that TLR4 signaling within the endothelium plays an essential role in NEC development by regulating perfusion to the small intestine via the vasodilatory molecule endothelial nitric oxide synthase (eNOS). Using a unique mouse system in which we selectively deleted TLR4 from the endothelium, we now show that endothelial TLR4 activation is required for NEC development and that endothelial TLR4 activation impairs intestinal perfusion without effects on other organs and reduces eNOS expression via activation of myeloid differentiation primary response gene 88. NEC severity was significantly increased in eNOS
−/−
mice and decreased upon administration of the phosphodiesterase inhibitor sildenafil, which augments eNOS function. Strikingly, compared with formula, human and mouse breast milk were enriched in sodium nitrate—a precursor for enteral generation of nitrite and nitric oxide—and repletion of formula with sodium nitrate/nitrite restored intestinal perfusion, reversed the deleterious effects of endothelial TLR4 signaling, and reduced NEC severity. These data identify that endothelial TLR4 critically regulates intestinal perfusion leading to NEC and reveal that the protective properties of breast milk involve enhanced intestinal microcirculatory integrity via augmentation of nitrate–nitrite–NO signaling.
Motile invaded neutrophils in the small intestine ofToxoplasma gondii-infected mice reveal a potential mechanism for parasite spread
Authors: Coombes Janine L. , Charsar Brittany A. , Han Seong-Ji , Halkias Joanna , Chan Shiao Wei , Koshy Anita A. , Striepen Boris , Robey Ellen A.
Published: May 2013

Significance

Toxoplasma gondiiinfection occurs following consumption of infected meat or contaminated water and produce. As a result, the parasite first enters the body in the intestine, but we understand surprisingly little about how it behaves there. In this study, we show thatT. gondiican invade neutrophils in the intestine directly, hitching a ride in these cells as they migrate out of the intestinal tissue into the lumen. Our findings implicate neutrophils and other immune cells in a surprising luminal pathway for the spread of infection and suggest new targets for therapeutic intervention in oral infection.
Salts drive controllable multilayered upright assembly of amyloid-like peptides at mica/water interface
Authors: Dai Bin , Kang Seung-gu , Huynh Tien , Lei Haozhi , Castelli Matteo , Hu Jun , Zhang Yi , Zhou Ruhong
Published: May 2013

Surface-assisted self-assembly of amyloid-like peptides has received considerable interest in both amyloidosis research and nanotechnology in recent years. Despite extensive studies, some controlling factors, such as salts, are still not well understood, even though it is known that some salts can promote peptide self-assemblies through the so-called “salting-out” effect. However, they are usually noncontrollable, disordered, amorphous aggregates. Here, we show via a combined experimental and theoretical approach that a conserved consensus peptide NH
2
-VGGAVVAGV-CONH
2
(GAV-9) (from representative amyloidogenic proteins) can self-assemble into highly ordered, multilayered nanofilaments, with surprising all-upright conformations, under high-salt concentrations. Our atomic force microscopy images also demonstrate that the vertical stacking of multiple layers is highly controllable by tuning the ionic strength, such as from 0 mM (monolayer) to 100 mM (mainly double layer), and to 250 mM MgCl
2
(double, triple, quadruple, and quintuple layers). Our atomistic molecular dynamics simulations then reveal that these individual layers have very different internal nanostructures, with parallel β-sheets in the first monolayer but antiparallel β-sheets in the subsequent upper layers due to their different microenvironment. Further studies show that the growth of multilayered, all-upright nanostructures is a common phenomenon for GAV-9 at the mica/water interface, under a variety of salt types and a wide range of salt concentrations.
WRKY8 transcription factor functions in the TMV-cg defense response by mediating both abscisic acid and ethylene signaling in
Arabidopsis
Authors: Chen Ligang , Zhang Liping , Li Daibo , Wang Fang , Yu Diqiu
Published: May 2013

Significance

Previous studies have shown that abscisic acid (ABA) has a positive effect on virus infection, and ethylene has a negative effect. However, the possible crosstalk between ABA and ethylene signaling during plants–virus interaction remains unclear. Our current results demonstrate that WRKY8 is involved in the defense response against crucifer-infecting tobacco mosaic virus (TMV-cg) through the direct regulation of the expression of
ABI4
,
ACS6
, and
ERF104
and thus may mediate the crosstalk between ABA and ethylene signaling during the TMV-cg–Arabidopsis interaction.
Mesenchymal glioma stem cells are maintained by activated glycolytic metabolism involving aldehyde dehydrogenase 1A3
Authors: Mao Ping , Joshi Kaushal , Li Jianfeng , Kim Sung-Hak , Li Peipei , Santana-Santos Lucas , Luthra Soumya , Chandran Uma R. , Benos Panayiotis V. , Smith Luke , Wang Maode , Hu Bo , Cheng Shi-Yuan , Sobol Robert W. , Nakano Ichiro
Published: May 2013

Tumor heterogeneity of high-grade glioma (HGG) is recognized by four clinically relevant subtypes based on core gene signatures. However, molecular signaling in glioma stem cells (GSCs) in individual HGG subtypes is poorly characterized. Here we identified and characterized two mutually exclusive GSC subtypes with distinct dysregulated signaling pathways. Analysis of mRNA profiles distinguished proneural (PN) from mesenchymal (Mes) GSCs and revealed a pronounced correlation with the corresponding PN or Mes HGGs. Mes GSCs displayed more aggressive phenotypes in vitro and as intracranial xenografts in mice. Further, Mes GSCs were markedly resistant to radiation compared with PN GSCs. The glycolytic pathway, comprising aldehyde dehydrogenase (ALDH) family genes and in particular ALDH1A3, were enriched in Mes GSCs. Glycolytic activity and ALDH activity were significantly elevated in Mes GSCs but not in PN GSCs. Expression of ALDH1A3 was also increased in clinical HGG compared with low-grade glioma or normal brain tissue. Moreover, inhibition of ALDH1A3 attenuated the growth of Mes but not PN GSCs. Last, radiation treatment of PN GSCs up-regulated Mes-associated markers and down-regulated PN-associated markers, whereas inhibition of ALDH1A3 attenuated an irradiation-induced gain of Mes identity in PN GSCs. Taken together, our data suggest that two subtypes of GSCs, harboring distinct metabolic signaling pathways, represent intertumoral glioma heterogeneity and highlight previously unidentified roles of ALDH1A3-associated signaling that promotes aberrant proliferation of Mes HGGs and GSCs. Inhibition of ALDH1A3-mediated pathways therefore might provide a promising therapeutic approach for a subset of HGGs with the Mes signature.
Specialized bat tongue is a hemodynamic nectar mop
Authors: Harper Cally J. , Swartz Sharon M. , Brainerd Elizabeth L.
Published: May 2013

Nectarivorous birds and bats have evolved highly specialized tongues to gather nectar from flowers. Here, we show that a nectar-feeding bat,
Glossophaga soricina
, uses dynamic erectile papillae to collect nectar. In
G. soricina
, the tip of the tongue is covered with long filamentous papillae and resembles a brush or mop. During nectar feeding, blood vessels within the tongue tip become engorged with blood and the papillae become erect. Tumescence and papilla erection persist throughout tongue retraction, and nectar, trapped between the rows of erect papillae, is carried into the mouth. The tongue tip does not increase in overall volume as it elongates, suggesting that muscle contraction against the tongue’s fixed volume (i.e., a muscular hydrostat) is primarily responsible for tip elongation, whereas papilla erection is a hydraulic process driven by blood flow. The hydraulic system is embedded within the muscular hydrostat, and, thus, intrinsic muscle contraction may simultaneously increase the length of the tongue and displace blood into the tip. The tongue of
G. soricina
, together with the tongues of nectar-feeding bees and hummingbirds, which also have dynamic surfaces, could serve as valuable models for developing miniature surgical robots that are both protrusible and have highly dynamic surface configurations.
Kif7
is required for the patterning and differentiation of the diaphragm in a model of syndromic congenital diaphragmatic hernia
Authors: Coles Garry L. , Ackerman Kate G.
Published: May 2013

Significance

Human congenital diaphragmatic defects are almost as common as cystic fibrosis, cause neonatal mortality, and often result in multisystem morbidity throughout childhood. Research investigating mechanisms of development is needed to understand the pathogenesis of disease. In this report, we identified a model caused by a mutation in kinesin motor family gene
kinesin family member 7
. We determined that this gene is required to regulate cell proliferation, patterning, and differentiation in the embryonic diaphragm. We ascertained several functions of retinoid signaling in diaphragm development and gained insight into how perturbations in this signaling network promote the pathogenesis of congenital diaphragmatic hernia.
Expression of recombinant human complement C1q allows identification of the C1r/C1s-binding sites
Authors: Bally Isabelle , Ancelet Sarah , Moriscot Christine , Gonnet Florence , Mantovani Alberto , Daniel Régis , Schoehn Guy , Arlaud Gérard J. , Thielens Nicole M.
Published: May 2013

Complement C1q is a hexameric molecule assembled from 18 polypeptide chains of three different types encoded by three genes. This versatile recognition protein senses a wide variety of immune and nonimmune ligands, including pathogens and altered self components, and triggers the classical complement pathway through activation of its associated proteases C1r and C1s. We report a method for expression of recombinant full-length human C1q involving stable transfection of HEK 293-F mammalian cells and fusion of an affinity tag to the C-terminal end of the C chain. The resulting recombinant (r) C1q molecule is similar to serum C1q as judged from biochemical and structural analyses and exhibits the characteristic shape of a bunch of flowers. Analysis of its interaction properties by surface plasmon resonance shows that rC1q retains the ability of serum C1q to associate with the C1s-C1r-C1r-C1s tetramer, to recognize physiological C1q ligands such as IgG and pentraxin 3, and to trigger C1r and C1s activation. Functional analysis of rC1q variants carrying mutations of LysA59, LysB61, and/or LysC58, in the collagen-like stems, demonstrates that LysB61 and LysC58 each play a key role in the interaction with C1s-C1r-C1r-C1s, with LysA59 being involved to a lesser degree. We propose that LysB61 and LysC58 both form salt bridges with outer acidic Ca
2+
ligands of the C1r and C1s CUB (complement C1r/C1s, Uegf, bone morphogenetic protein) domains. The expression method reported here opens the way for deciphering the molecular basis of the unusual binding versatility of C1q by mapping the residues involved in the sensing of its targets and the binding of its receptors.
Structural plasticity of the cellular prion protein and implications in health and disease
Authors: Christen Barbara , Damberger Fred F. , Pérez Daniel R. , Hornemann Simone , Wüthrich Kurt
Published: May 2013

Two lines of transgenic mice expressing mouse/elk and mouse/horse prion protein (PrP) hybrids, which both form a well-structured β2–α2 loop in the NMR structures at 20 °C termed rigid-loop cellular prion proteins (RL-PrP
C
), presented with accumulation of the aggregated scrapie form of PrP in brain tissue, and the mouse/elk hybrid has also been shown to develop a spontaneous transmissible spongiform encephalopathy. Independently, there is in vitro evidence for correlations between the amino acid sequence in the β2–α2 loop and the propensity for conformational transitions to disease-related forms of PrP. To further contribute to the structural basis for these observations, this paper presents a detailed characterization of RL-PrP
C
conformations in solution. A dynamic local conformational polymorphism involving the β2–α2 loop was found to be evolutionarily preserved among all mammalian species, including those species for which the WT PrP forms an RL-PrP
C
. The interconversion between two ensembles of PrP
C
conformers that contain, respectively, a 3
10
-helix turn or a type I β-turn structure of the β2–α2 loop, exposes two different surface epitopes, which are analyzed for their possible roles in the still evasive function of PrP
C
in healthy organisms and/or at the onset of a transmissible spongiform encephalopathy.
Fluorescence thermometry enhanced by the quantum coherence of single spins in diamond
Authors: Toyli David M. , de las Casas Charles F. , Christle David J. , Dobrovitski Viatcheslav V. , Awschalom David D.
Published: May 2013

We demonstrate fluorescence thermometry techniques with sensitivities approaching 10 mK⋅Hz
−1/2
based on the spin-dependent photoluminescence of nitrogen vacancy (NV) centers in diamond. These techniques use dynamical decoupling protocols to convert thermally induced shifts in the NV center's spin resonance frequencies into large changes in its fluorescence. By mitigating interactions with nearby nuclear spins and facilitating selective thermal measurements, these protocols enhance the spin coherence times accessible for thermometry by 45-fold, corresponding to a 7-fold improvement in the NV center’s temperature sensitivity. Moreover, we demonstrate these techniques can be applied over a broad temperature range and in both finite and near-zero magnetic field environments. This versatility suggests that the quantum coherence of single spins could be practically leveraged for sensitive thermometry in a wide variety of biological and microscale systems.
The posttranslational modification cascade to the thiopeptide berninamycin generates linear forms and altered macrocyclic scaffolds
Authors: Malcolmson Steven J. , Young Travis S. , Ruby J. Graham , Skewes-Cox Peter , Walsh Christopher T.
Published: May 2013

Berninamycin is a member of the pyridine-containing thiopeptide class of antibiotics that undergoes massive posttranslational modifications from ribosomally generated preproteins. Berninamycin has a 2-oxazolyl-3-thiazolyl-pyridine core embedded in a 35-atom macrocycle rather than typical trithiazolylpyridine cores embedded in 26-atom and 29-atom peptide macrocycles. We describe the cloning of an 11-gene berninamycin cluster from
Streptomyces bernensis
UC 5144, its heterologous expression in
Streptomyces lividans
TK24 and
Streptomyces venezuelae
ATCC 10712, and detection of variant and incompletely processed scaffolds. Posttranslational maturation in
S. lividans
of both the wild-type berninamycin prepeptide (BerA) and also a T3A mutant generates macrocyclic compounds as well as linear variants, which have failed to form the pyridine and the macrocycle. Expression of the gene cluster in
S. venezuelae
generates a variant of the 35-atom skeleton of berninamycin, containing a methyloxazoline in the place of a methyloxazole within the macrocyclic framework.
Psychologists' and counsellors' perspectives on prolonged grief disorder and its inclusion in diagnostic manuals
Authors: Ogden Shelley Patricia , Simmonds Janette Graetz
Published: May 2013

Introduction: In this research, proposed criteria for what has been termed ‘Prolonged Grief Disorder’ (PGD) (more recently termed, ‘Persistent Complex Bereavement‐Related Disorder’ (PCB‐RD) in the proposed DSM‐V), were presented to psychologists and counsellors. Method: Participants were asked about their views on the ‘disorder’ and whether they considered its inclusion in diagnostic manuals was justified. A total of 185 participants, (147 psychologists, specialist and general, and 38 counsellors) responded to an online survey (part of a larger research project), concerning their attitudes, choices and activities regarding bereavement therapy. In this part of the research, therapists’ perspectives about pathological grief, the recognition of PGD and its inclusion in diagnostic manuals were explored. Fifty‐nine participants took the option of adding written remarks to the survey to expand on their opinions regarding PGD. Results/Conclusions: Tentative support for the inclusion of PGD in diagnostic manuals was given; however many therapists indicated considerable reservations about potential negative repercussions of using such a diagnosis. One‐way between‐groups analysis of variance was undertaken to determine whether participants' opinions varied according to main occupation or specialism; however, no significant difference was found. This research was conducted prior to the latest update to the proposed revision and diagnostic category concerning bereavement in the DSM‐5 of April 2012, but many observations and recommendations concerning PGD made by the therapists participating in this research can be seen to be applicable to PCB‐RD. Implications: The implications of this research for assessing and diagnosing grief, and ways of working with bereaved clients, are discussed.
Gain-of-function mutations of PPM1D/Wip1 impair the p53-dependent G1 checkpoint
Authors: Kleiblova Petra , Shaltiel Indra A. , Benada Jan , Ševčík Jan , Pecháčková Soňa , Pohlreich Petr , Voest Emile E. , Dundr Pavel , Bartek Jiri , Kleibl Zdenek , Medema René H. , Macurek Libor
Published: May 2013

The DNA damage response (DDR) pathway and its core component tumor suppressor p53 block cell cycle progression after genotoxic stress and represent an intrinsic barrier preventing cancer development. The serine/threonine phosphatase PPM1D/Wip1 inactivates p53 and promotes termination of the DDR pathway. Wip1 has been suggested to act as an oncogene in a subset of tumors that retain wild-type p53. In this paper, we have identified novel gain-of-function mutations in exon 6 of PPM1D that result in expression of C-terminally truncated Wip1. Remarkably, mutations in PPM1D are present not only in the tumors but also in other tissues of breast and colorectal cancer patients, indicating that they arise early in development or affect the germline. We show that mutations in PPM1D affect the DDR pathway and propose that they could predispose to cancer.
Making short work of p53
Authors: Leslie Mitch
Published: May 2013

A truncated phosphatase shuts down genome guardian in tumor cells.
CANDELS MULTIWAVELENGTH CATALOGS: SOURCE IDENTIFICATION AND
PHOTOMETRY IN THE CANDELS UKIDSS ULTRA-DEEP SURVEY FIELD
Authors: Galametz Audrey , Grazian Andrea , Fontana Adriano , Ferguson Henry C. , Ashby M. L. N. , Barro Guillermo , Castellano Marco , Dahlen Tomas , Donley Jennifer L. , Faber Sandy M. , Grogin Norman , Guo Yicheng , Huang Kuang-Han , Kocevski Dale D. , Koekemoer Anton M. , Lee Kyoung-Soo , McGrath Elizabeth J. , Peth Michael , Willner S. P. , Almaini Omar , Cooper Michael , Cooray Asantha , Conselice Christopher J. , Dickinson Mark , Dunlop James S. , Fazio G. G. , Foucaud Sebastien , Gardner Jonathan P. , Giavalisco Mauro , Hathi N. P. , Hartley Will G. , Koo David C. , Lai Kamson , de Mello Duilia F. , McLure Ross J. , Lucas Ray A. , Paris Diego , Pentericci Laura , Santini Paola , Simpson Chris , Sommariva Veronica , Targett Thomas , Weiner Benjamin J. , Wuyts Stijn
Published: May 2013

We present the multiwavelength—ultraviolet to mid-infrared—catalog of the UKIRT
Infrared Deep Sky Survey (UKIDSS) Ultra-Deep Survey field observed as part of
the Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS).
Based on publicly available data, the catalog includes the CANDELS data from the
Hubble
Space Telescope (near-infrared WFC3
F125W and
F160W data and visible ACS
F606W and
F814W data); u-band data
from CFHT/Megacam; B, V,
Rc
, i′, and z′
band data from Subaru/Suprime-Cam; Y and
Ks
band data from VLT/HAWK-I;
J, H, and K band data from
UKIDSS (Data Release 8); and Spitzer/IRAC data (3.6, 4.5 μm
from SEDS; 5.8 and 8.0 μm from SpUDS). The present catalog is
F160W-selected and contains 35, 932
sources over an area of 201.7 arcmin2 and includes radio- and
X-ray-detected sources and spectroscopic redshifts available for 210
sources.
Effects of Steam, Moisture, and Screw Speed on Physical Properties of DDGS‐Based Extrudates
Authors: Fallahi Parisa , Rosentrater Kurt A. , Muthukumarappan Kasiviswanathan , Tulbek Mehmet
Published: May 2013

A fractional factorial design with a replicated central composite point was used to investigate the effects of extrusion processing on physical properties of distillers dried grains with solubles (DDGS) based aquafeeds using a twin‐screw extruder. Extrusion cooking trials were performed with a nutritionally balanced ingredient blend for Nile tilapia, with two levels of screw speed (350 and 450 rpm), two levels of extruder water (0.236 and 0.302 kg/min), and two levels of conditioner steam (0.1 and 0.15 kg/min). The central point was 400 rpm screw speed, 0.271 kg/min extruder water, and 0.12 kg/min conditioner steam. Effects of these processing conditions on extrudate characteristics were extensively analyzed and included moisture content, water activity, thermal properties, expansion ratio, unit density, bulk density, color, water stability, sinking velocity, water absorption and solubility indices, and pellet durability index. Increasing the extruder water and conditioner steam resulted in a 5.3% decrease and nearly 8.6% rise in mass flow rate, respectively. As screw speed increased from 350 to 400 rpm, water stability and water activity increased by 13 and 58%, respectively. Increasing extruder water from 0.236 to 0.302 kg/min led to a significant increase in water stability by 12.5% and decreases in water absorption index, water activity, and expansion ratio by 13, 21, and 5.5%, respectively. As conditioner steam increased from 0.1 to 0.15 kg/min, sinking velocity and water absorption index decreased by 25 and 15%, respectively. Increasing conditioner steam from 0.1 to 0.12 kg/min resulted in 20, 5.5, 10, and 3% decreases in moisture content of the extrudates, brightness (L*), water stability, and expansion ratio, respectively. It also increased bulk density by 5.8% and unit density by 4.2%. Overall, all trials produced viable extrudates with properties appropriate for Nile tilapia feeding.
High-resolution analysis of
cis
-acting regulatory networks at the α-globin locus
Authors: Hughes Jim R. , Lower Karen M. , Dunham Ian , Taylor Stephen , De Gobbi Marco , Sloane-Stanley Jacqueline A. , McGowan Simon , Ragoussis Jiannis , Vernimmen Douglas , Gibbons Richard J. , Higgs Douglas R.
Published: May 2013

We have combined the circular chromosome conformation capture protocol with high-throughput, genome-wide sequence analysis to characterize the
cis
-acting regulatory network at a single locus. In contrast to methods which identify large interacting regions (10–1000 kb), the 4C approach provides a comprehensive, high-resolution analysis of a specific locus with the aim of defining, in detail, the
cis
-regulatory elements controlling a single gene or gene cluster. Using the human α-globin locus as a model, we detected all known local and long-range interactions with this gene cluster. In addition, we identified two interactions with genes located 300 kb (NME4) and 625 kb (FAM173a) from the α-globin cluster.
Deconvoluting complex tissues for expression quantitative trait locus-based analyses
Authors: Seo Ji-Heui , Li Qiyuan , Fatima Aquila , Eklund Aron , Szallasi Zoltan , Polyak Kornelia , Richardson Andrea L. , Freedman Matthew L.
Published: May 2013

Breast cancer genome-wide association studies have pinpointed dozens of variants associated with breast cancer pathogenesis. The majority of risk variants, however, are located outside of known protein-coding regions. Therefore, identifying which genes the risk variants are acting through presents an important challenge. Variants that are associated with mRNA transcript levels are referred to as expression quantitative trait loci (eQTLs). Many studies have demonstrated that eQTL-based strategies provide a direct way to connect a trait-associated locus with its candidate target gene. Performing eQTL-based analyses in human samples is complicated because of the heterogeneous nature of human tissue. We addressed this issue by devising a method to computationally infer the fraction of cell types in normal human breast tissues. We then applied this method to 13 known breast cancer risk loci, which we hypothesized were eQTLs. For each risk locus, we took all known transcripts within a 2 Mb interval and performed an eQTL analysis in 100 reduction mammoplasty cases. A total of 18 significant associations were discovered (eight in the epithelial compartment and 10 in the stromal compartment). This study highlights the ability to perform large-scale eQTL studies in heterogeneous tissues.
The DEAH-box helicase DHX36 mediates dendritic localization of the neuronal precursor-microRNA-134
Authors: Bicker Silvia , Khudayberdiev Sharof , Weiß Kerstin , Zocher Kathleen , Baumeister Stefan , Schratt Gerhard
Published: May 2013

Specific microRNAs (miRNAs), including miR-134, localize to neuronal dendrites, where they control synaptic protein synthesis and plasticity. However, the mechanism of miRNA transport is unknown. We found that the neuronal precursor-miRNA-134 (pre-miR-134) accumulates in dendrites of hippocampal neurons and at synapses in vivo. Dendritic localization of pre-miR-134 is mediated by the DEAH-box helicase DHX36, which directly associates with the pre-miR-134 terminal loop. DHX36 function is required for miR-134-dependent inhibition of target gene expression and the control of dendritic spine size. Dendritically localized pre-miR-134 could provide a local source of miR-134 that can be mobilized in an activity-dependent manner during plasticity.
Genome-wide RNAi screens in human brain tumor isolates reveal a novel viability requirement for PHF5A
Authors: Hubert Christopher G. , Bradley Robert K. , Ding Yu , Toledo Chad M. , Herman Jacob , Skutt-Kakaria Kyobi , Girard Emily J. , Davison Jerry , Berndt Jason , Corrin Philip , Hardcastle Justin , Basom Ryan , Delrow Jeffery J. , Webb Thomas , Pollard Steven M. , Lee Jeongwu , Olson James M. , Paddison Patrick J.
Published: May 2013

To identify key regulators of human brain tumor maintenance and initiation, we performed multiple genome-wide RNAi screens in patient-derived glioblastoma multiforme (GBM) stem cells (GSCs). These screens identified the plant homeodomain (PHD)-finger domain protein PHF5A as differentially required for GSC expansion, as compared with untransformed neural stem cells (NSCs) and fibroblasts. Given PHF5A's known involvement in facilitating interactions between the U2 snRNP complex and ATP-dependent helicases, we examined cancer-specific roles in RNA splicing. We found that in GSCs, but not untransformed controls, PHF5A facilitates recognition of exons with unusual C-rich 3′ splice sites in thousands of essential genes. PHF5A knockdown in GSCs, but not untransformed NSCs, astrocytes, or fibroblasts, inhibited splicing of these genes, leading to cell cycle arrest and loss of viability. Notably, pharmacologic inhibition of U2 snRNP activity phenocopied PHF5A knockdown in GSCs and also in NSCs or fibroblasts overexpressing MYC. Furthermore, PHF5A inhibition compromised GSC tumor formation in vivo and inhibited growth of established GBM patient-derived xenograft tumors. Our results demonstrate a novel viability requirement for PHF5A to maintain proper exon recognition in brain tumor-initiating cells and may provide new inroads for novel anti-GBM therapeutic strategies.
The family that eats together stays together: new p53 family transcriptional targets in autophagy
Authors: Napoli Marco , Flores Elsa R.
Published: May 2013

Autophagy is a biological process that is crucial to maintain cellular homeostasis and is regulated by several metabolic pathways, including the p53 tumor suppressor pathway. In this issue of Genes & Development, Kenzelmann Broz and colleagues (pp. 1016–1031) show how the p53 family as a whole, including p63 and p73, collaborate in controlling autophagy to support tumor suppression.
Protein segregase meddles in remodeling of mRNA–protein complexes
Authors: Chen Chyi-Ying A. , Shyu Ann-Bin
Published: May 2013

Remodeling of RNA–protein complexes (mRNPs) plays a critical role in mRNA biogenesis and metabolism. However, relatively little is known about the underlying mechanism and regulation of the mRNP remodeling. In this issue of Genes & Development, Zhou and colleagues (pp. 1046–1058) report that a protein remodeling machine, the p97–UBXD8 complex, disassembles mRNPs containing the AU-rich elements (AREs) bound by HuR proteins in a nondegradative, ubiquitin signaling-dependent manner, revealing a novel mechanism to regulate mRNA turnover.
Genetic analysis of ORF5 porcine reproductive and respiratory syndrome virus isolated in Vietnam
Authors: Thi Dieu Thuy Nguyen , Thi Thu Nguyen , Son Nguyen Giang , Ha Le Thi Thu , Hung Vo Khanh , Nguyen Nguyen Thao , Khoa Do Vo Anh
Published: May 2013

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important swine pathogens because it is highly infectious and causes economic losses due to decreased pig productivity. In this study, the 603 bp complete major envelope protein encoding gene (ORF5) of 32 field PRRSV isolates from Vietnam collected during 2008–2012 were sequenced and analyzed. Multiple nucleotide (nt) and deduced amino acid (aa) alignments of ORF5 were performed on the 32 isolates: the representative strains (European and North American genotypes), Chinese strains available in GenBank and vaccine strains licensed for use in Vietnam. The results showed 94.8–100.0% nt identity and 94.0–100% aa similarity among the 32 isolates. These isolates shared similarities with the prototype of the North American PRRSV strain (VR‐2332; nt 87.8–89.3%, aa 87.5–90.0%), and Lelystat virus, the prototype of the European PRRSV strain (LV; nt 61.1–61.9%, aa 55.1‐57.0%). There was greater similarity with QN07 (nt 96.5‐98.5%, aa 96.0‐99.0%) from the 2007 PRRS outbreak in QuangNam Province, CH‐1a (nt 93.2–95.1%, 91.5–93.5%) isolated in China in 1995 and JXA1 (nt 96.5–98.6%, aa 95.0–98.0%), the highly pathogenic strain from China isolated in 2006. The Vietnamese isolates were more similar to JXA1‐R (nt 96.5–98.6%, aa 95.0–98.0%), the strain used in Chinese vaccines, than to Ingelvac MLV/BSL‐PS (nt 87.2–89.0%, aa 86.0–89.0%). Phylogenetic analysis showed that the 32 isolates were of the North American genotype and classified into sub‐lineage 8.7. This sub‐lineage contains highly pathogenic Chinese PRRSV strains. This study documents genetic variation in circulating PRRSV strains and could assist more effective use of PRRS vaccines in Vietnam.
Fruit bats and bat fruits: the evolution of fruit scent in relation to the foraging behaviour of bats in the New and Old World tropics
Authors: Hodgkison Robert , Ayasse Manfred , Häberlein Christopher , Schulz Stefan , Zubaid Akbar , Mustapha Wan Aida W. , Kunz Thomas H. , Kalko Elisabeth K. V.
Published: May 2013

Frugivory among bats (Chiroptera) has evolved independently in the New and Old World tropics: within the families Phyllostomidae and Pteropodidae, respectively. Bats from both families rely primarily on olfaction for the location of fruits. However, the influence of bats on the evolution of fruit scent is almost completely unknown.

Using the genusFicusas a model, the aims of this study were to explore the chemical composition of fruit scent in relation to two contrasting seed dispersal syndromes in Panama and Malaysia and to assess the influence of fruit scent on the foraging behaviour of neo‐ and palaeotropical fruit‐eating bats (Artibeus jamaicensisandCynopterus brachyotis, respectively). Two hypotheses were tested: (i) variation in fruit scent, between bat‐ and bird‐dispersed figs, is independent of phylogeny and (ii) Old and New World fruit bats, which have evolved independently in each hemisphere, share the same olfactory preferences with respect to fruit scent.

The fruit scents of bat‐ and bird‐dispersed fig species were sampled in the field, using dynamic headspace adsorption techniques. New and Old World fruit bats were then captured and tested on natural fig fruit scents from both hemispheres.

Chemical analyses, using gas chromatography (GC) andGC/mass spectrometry (MS), revealed a broad overlap in scent compounds between bat‐dispersed fig species from both hemispheres. Their fruit scents were dominated by monoterpenes, which contrary to phylogenetic predictions, were completely absent from bird‐dispersed species from both regions.

The fruit scents of bat‐dispersed figs were highly attractive to neotropical bats (A. jamaicensis) in behavioural experiments, whereas those of bird‐dispersed figs were completely rejected. Neotropical bats (A. jamaicensis) exhibited a significant preference for fig fruit scents dominated by monoterpenes, independent of the geographical origin of the scent. Palaeotropical bats (C. brachyotis), by contrast, rejected monoterpene‐rich fruit scents from the Neotropics.

In a cluster analysis (which included additional, published data from the literature), the fruit scents of bat‐dispersed figs were clumped by subgenus, with the exception of palaeotropical figs of the subgenus Sycomorus.C. brachyotis, from Malaysia, was the only fruit bat species that significantly preferred the fruit scents of Sycomorus figs that contained no monoterpenes.
How do foragers decide when to leave a patch? A test of alternative models under natural and experimental conditions
Authors: Marshall Harry H. , Carter Alecia J. , Ashford Alexandra , Rowcliffe J. Marcus , Cowlishaw Guy
Published: May 2013

A forager's optimal patch‐departure time can be predicted by the prescient marginal value theorem (pMVT), which assumes they have perfect knowledge of the environment, or by approaches such as Bayesian updating and learning rules, which avoid this assumption by allowing foragers to use recent experiences to inform their decisions.

In understanding and predicting broader scale ecological patterns, individual‐level mechanisms, such as patch‐departure decisions, need to be fully elucidated. Unfortunately, there are few empirical studies that compare the performance of patch‐departure models that assume perfect knowledge with those that do not, resulting in a limited understanding of how foragers decide when to leave a patch.

We tested the patch‐departure rules predicted by fixed rule, pMVT, Bayesian updating and learning models against one another, using patch residency times (PRTs) recorded from 54 chacma baboons (Papio ursinus) across two groups in natural (n = 6175 patch visits) and field experimental (n = 8569) conditions.

We found greater support in the experiment for the model based on Bayesian updating rules, but greater support for the model based on the pMVT in natural foraging conditions. This suggests that foragers may place more importance on recent experiences in predictable environments, like our experiment, where these experiences provide more reliable information about future opportunities.

Furthermore, the effect of a single recent foraging experience on PRTs was uniformly weak across both conditions. This suggests that foragers’ perception of their environment may incorporate many previous experiences, thus approximating the perfect knowledge assumed by the pMVT. Foragers may, therefore, optimize their patch‐departure decisions in line with the pMVT through the adoption of rules similar to those predicted by Bayesian updating.
Pollination biology of the endangered orchid Cypripedium japonicum in a fragmented forest of Japan
Authors: Suetsugu Kenji , Fukushima Shigeki
Published: May 2013

Pollination biology studies of the endangered orchid Cypripedium japonicum were conducted in its natural habitat using pollinator observation and hand‐pollination experiments. The observed fruit set was as follows: artificial outcross‐pollinated, 100%; artificial self‐pollinated, 100%; pollinator‐excluded, 0%; and emasculated flowers, 0%. These results show that this species, although self‐compatible, is neither autogamous nor agamospermous. The fruit set for open‐pollinated flowers was 14.9%, which suggests that the study population was subject to pollinator limitation. The nectarless flowers of C. japonicum were exclusively visited and pollinated by the queens of two bumblebee species (Bombus ardens and B. diversus diversus). It is probable that the nectarless flowers of C. japonicum attract pollinators through a generalized food deceptive system.
Antiphospholipid Antibodies Affect Human Endometrial Angiogenesis: Protective Effect of a Synthetic Peptide (TIFI) Mimicking the Phospholipid Binding Site of β2glycoprotein I
Authors: Di Simone Nicoletta , D'Ippolito Silvia , Marana Riccardo , Di Nicuolo Fiorella , Castellani Roberta , Pierangeli Silvia S. , Chen Pojen , Tersigni Chiara , Scambia Giovanni , Meroni Pier Luigi
Published: May 2013

Problem

Aim of our study was to investigate whether TIFI, a syntetic peptide able to compete with anti‐phospholipid antibodies (aPL) in the binding to endothelium, may restore aPL‐inhibited endometrial angiogenesis.

Methods

The protective role of TIFI was evaluated on: i) aPL–inhibited of human endometrial endothelial cells (HEEC) angiogenesis in vitro; ii) aPL–inhibited vascular endothelial growth factor (VEGF) and metalloproteases (MMPs) expression; iii) aPL‐inhibited Nuclear Factor‐κB (NF‐κB) and Extracellular signal–Regulated Kinase (ERK) activation and (iv) angiogenesis in vivo.

Results

TIFI restores in a dose‐dependent manner: i) aPL‐mediated inhibition of HEEC angiogenesis in vitro and in vivo (P < 0.05), ii) VEGF (P < 0.001) and MMP–2 (P < 0.05) expression and iii) NF‐κB DNA binding and ERK–1/2 activation (P < 0.05) inhibited by aPL.

Conclusion

Our results show for the first time the protective effects of TIFI, as represented by its ability to interfere with aPL mediated anti‐angiogenic activity.
Constriction of porcine retinal arterioles induced by endothelin‐1 and the thromboxane analogue U46619 in vitro decreases with increasing vascular branching level
Authors: Torring Maria Skytte , Aalkjaer Christian , Bek Toke
Published: May 2013

Purpose:  The retinal blood flow depends on the diameter of retinal arterioles, but diameter changes in these vessels have hitherto only been assessed in vessels larger than approximately 100 μm. Therefore, a new method was developed for studying diameter changes along the vascular tree of arterioles in whole perfused segments of porcine retinas, and the effect of known vasoconstrictors on the diameter of retinal arterioles at different branching levels were studied.

Methods:  Thirty‐four whole‐mounted porcine retinas were placed in a specially designed tissue chamber. On the basis of video recordings through an inverted microscope, the diameter of retinal arterioles was measured at five different branching levels before and after addition of a high potassium concentration, or increasing concentrations of endothelin‐1, the prostaglandin analogue U46619, noradrenaline or none (time controls).

Results:  The baseline diameter ranged from 136 μm (95% CI 132–140 μm) for 1st order arterioles to 33 μm (95% CI 21–44 μm) for 5th order arterioles. In 1st order arterioles, endothelin produced 56.6% (95% CI 47.6–64.0) and U46619 14.6% (95% CI 5.7–22.6) relative constriction compared with baseline, which for both compounds decreased significantly with increasing branching level (p < 0.0001 and p < 0.0001, respectively). The change in diameter during addition of noradrenaline did not differ significantly from the time controls (p = 0.07).

Conclusions:  The effect of retinal vasoconstrictors differs among larger and smaller arterioles. The study highlights the need for investigating diameter regulation in smaller retinal arterioles as a basis for understanding normal and pathological changes in retinal blood flow.
Exploring Local Modifications for Constrained Meshes
Authors: Deng Bailin , Bouaziz Sofien , Deuss Mario , Zhang Juyong , Schwartzburg Yuliy , Pauly Mark
Published: May 2013

Mesh editing under constraints is a challenging task with numerous applications in geometric modeling, industrial design, and architectural form finding. Recent methods support constraint‐based exploration of meshes with fixed connectivity, but commonly lack local control. Because constraints are often globally coupled, a local modification by the user can have global effects on the surface, making iterative design exploration and refinement difficult. Simply fixing a local region of interest a priori is problematic, as it is not clear in advance which parts of the mesh need to be modified to obtain an aesthetically pleasing solution that satisfies all constraints. We propose a novel framework for exploring local modifications of constrained meshes. Our solution consists of three steps. First, a user specifies target positions for one or more vertices. Our algorithm computes a sparse set of displacement vectors that satisfies the constraints and yields a smooth deformation. Then we build a linear subspace to allow realtime exploration of local variations that satisfy the constraints approximately. Finally, after interactive exploration, the result is optimized to fully satisfy the set of constraints. We evaluate our framework on meshes where each face is constrained to be planar.
DuctTake: Spatiotemporal Video Compositing
Authors: Rüegg Jan , Wang Oliver , Smolic Aljoscha , Gross Markus
Published: May 2013

DuctTake is a system designed to enable practical compositing of multiple takes of a scene into a single video. Current industry solutions are based around object segmentation, a hard problem that requires extensive manual input and cleanup, making compositing an expensive part of the film‐making process. Our method instead composites shots together by finding optimal spatiotemporal seams using motion‐compensated 3D graph cuts through the video volume. We describe in detail the required components, decisions, and new techniques that together make a usable, interactive tool for compositing HD video, paying special attention to running time and performance of each section. We validate our approach by presenting a wide variety of examples and by comparing result quality and creation time to composites made by professional artists using current state‐of‐the‐art tools.
Removing the Noise in Monte Carlo Rendering with General Image Denoising Algorithms
Authors: Kalantari Nima Khademi , Sen Pradeep
Published: May 2013

Monte Carlo rendering systems can produce important visual effects such as depth of field, motion blur, and area lighting, but the rendered images suffer from objectionable noise at low sampling rates. Although years of research in image processing has produced powerful denoising algorithms, most of them assume that the noise is spatially‐invariant over the entire image and cannot be directly applied to denoise Monte Carlo rendering. In this paper, we propose a new approach that enables the use of any spatially‐invariant image denoising technique to remove the noise in Monte Carlo renderings. Our key insight is to use a noise estimation metric to locally identify the amount of noise in different parts of the image, coupled with a multilevel algorithm that denoises the image in a spatially‐varying manner using a standard denoising technique. We also propose a new way to perform adaptive sampling that uses the noise estimation metric to identify the noisy regions in which to place more samples. We show that our framework runs in a few seconds with modern denoising algorithms and produces results that outperform state‐of‐the‐art techniques in Monte Carlo rendering.
Bilateral Hermite Radial Basis Functions for Contour‐based Volume Segmentation
Authors: Ijiri Takashi , Yoshizawa Shin , Sato Yu , Ito Masaaki , Yokota Hideo
Published: May 2013

In this paper, we propose a novel contour‐based volume image segmentation technique. Our technique is based on an implicit surface reconstruction strategy, whereby a signed scalar field is generated from user‐specified contours. The key idea is to compute the scalar field in a joint spatial‐range domain (i.e., bilateral domain) and resample its values on an image manifold. We introduce a new formulation of Hermite radial basis function (HRBF) interpolation to obtain the scalar field in the bilateral domain. In contrast to previous implicit methods, bilateral HRBF (B‐HRBF) generates a segmentation boundary that passes through all contours, fits high‐contrast image edges if they exist, and has a smooth shape in blurred areas of images. We also propose an acceleration scheme for computing B‐HRBF to support a real‐time and intuitive segmentation interface. In our experiments, we achieved high‐quality segmentation results for regions of interest with high‐contrast edges and blurred boundaries.
Microhabitat use by southern brook trout (Salvelinus fontinalis) in a headwater North Carolina stream
Authors: Anglin Zachary W. , Grossman Gary D.
Published: May 2013

Brook trout are the one of the only Salvelinus species native to eastern North America and range from Canada to Georgia. Very little is known, however, about the ecology of the southern form of this species. We quantified microhabitat use of southern brook trout in Ball Creek NC, a third‐order stream, during six seasonal samples (summer 2010, autumn 2010, spring 2011, summer 2011, autumn 2011 and spring 2012). In general, trout preferentially occupied deeper microhabitats with lower mean velocities and higher amounts of erosional substrata than were randomly available. Older trout (1+ and 2+) occupied deeper microhabitats with lower mean velocities than yearling trout. These microhabitats typically represent ‘plunge pools’. Southern brook trout also occupied focal point velocities that were statistically indistinguishable from optimal velocities calculated for rainbow trout in the same system and thus may chose microhabitats that maximise net energy gain. Southern brook trout are found in isolated populations, and management strategies should focus on the preservation of plunge pool habitat for conservation of this subspecies.