bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryoelectron tomography reveals doublet-specific structures and unique interactions in the I1 dynein
Authors: Heuser Thomas , Barber Cynthia F. , Lin Jianfeng , Krell Jeremy , Rebesco Matthew , Porter Mary E. , Nicastro Daniela
Published: June 2012

Cilia and flagella are highly conserved motile and sensory organelles in eukaryotes, and defects in ciliary assembly and motility cause many ciliopathies. The two-headed I1 inner arm dynein is a critical regulator of ciliary and flagellar beating. To understand I1 architecture and function better, we analyzed the 3D structure and composition of the I1 dynein in
Chlamydomonas
axonemes by cryoelectron tomography and subtomogram averaging. Our data revealed several connections from the I1 dynein to neighboring structures that are likely to be important for assembly and/or regulation, including a tether linking one I1 motor domain to the doublet microtubule and doublet-specific differences potentially contributing to the asymmetrical distribution of dynein activity required for ciliary beating. We also imaged three I1 mutants and analyzed their polypeptide composition using 2D gel-based proteomics. Structural and biochemical comparisons revealed the likely location of the regulatory IC138 phosphoprotein and its associated subcomplex. Overall, our studies demonstrate that I1 dynein is connected to multiple structures within the axoneme, and therefore ideally positioned to integrate signals that regulate ciliary motility.
Functional isolation of activated and unilaterally phosphorylated heterodimers of ERBB2 and ERBB3 as scaffolds in ligand-dependent signaling
Authors: Zhang Qian , Park Euisun , Kani Kian , Landgraf Ralf
Published: June 2012

The EGFR (ERBB) family provides a model system for receptor signaling, oncogenesis, and the development of targeted therapeutics. Heterodimers of the ligand-binding–deficient ERBB2 (HER2) receptor and the kinase impaired ERBB3 (HER3) create a potent mitogenic signal, but the phosphorylation of ERBB2 in this context presents a challenge to established models of phosphorylation
in trans
. Higher order complexes of ERBB receptors have been observed biophysically and offer a theoretical route for ERBB2 phosphorylation, but it is not clear whether such complexes provide functionality beyond the constituent dimers. We now show that a previously selected inhibitory RNA aptamer that targets the extracellular domain (ECD) of ERBB3 acts by sterically disrupting these higher order interactions. Ligand binding, heterodimerization, phosphorylation of ERBB3, and AKT signaling are only minimally affected, whereas ERBB2 phosphorylation and MAPK signaling are selectively inhibited. The mapping of the binding site and creation of aptamer-resistant point mutants are consistent with a model of side-by-side oriented heterodimers to facilitate proxy phosphorylation, even at very low endogenous levels of receptors (below 10,000 receptors per cell). Additional modes of signaling with relevance to pathological ERBB expression states emerge at high receptor levels. Hence, higher order complexes of nonoverexpressed ERBB receptors are an integral and qualitatively distinct part of normal ERBB2/ERBB3 signaling. This mechanism of activation has implications for models of allosteric control, specificity of interactions, possible mechanisms of cross-talk, and approaches to therapeutic intervention that at present often generate experimental and clinical outcomes that do not reconcile with purely canonical, dimer-based models.
Number sense across the lifespan as revealed by a massive Internet-based sample
Authors: Halberda Justin , Ly Ryan , Wilmer Jeremy B. , Naiman Daniel Q. , Germine Laura
Published: June 2012

It has been difficult to determine how cognitive systems change over the grand time scale of an entire life, as few cognitive systems are well enough understood; observable in infants, adolescents, and adults; and simple enough to measure to empower comparisons across vastly different ages. Here we address this challenge with data from more than 10,000 participants ranging from 11 to 85 years of age and investigate the precision of basic numerical intuitions and their relation to students’ performance in school mathematics across the lifespan. We all share a foundational number sense that has been observed in adults, infants, and nonhuman animals, and that, in humans, is generated by neurons in the intraparietal sulcus. Individual differences in the precision of this evolutionarily ancient number sense may impact school mathematics performance in children; however, we know little of its role beyond childhood. Here we find that population trends suggest that the precision of one’s number sense improves throughout the school-age years, peaking quite late at ∼30 y. Despite this gradual developmental improvement, we find very large individual differences in number sense precision among people of the same age, and these differences relate to school mathematical performance throughout adolescence and the adult years. The large individual differences and prolonged development of number sense, paired with its consistent and specific link to mathematics ability across the age span, hold promise for the impact of educational interventions that target the number sense.
Amniotic fluid inhibits Toll-like receptor 4 signaling in the fetal and neonatal intestinal epithelium
Authors: Good Misty , Siggers Richard H. , Sodhi Chhinder P. , Afrazi Amin , Alkhudari Feras , Egan Charlotte E. , Neal Matthew D. , Yazji Ibrahim , Jia Hongpeng , Lin Joyce , Branca Maria F. , Ma Congrong , Prindle Thomas , Grant Zachary , Shah Sapana , Slagle Dennis , Paredes Jose , Ozolek John , Gittes George K. , Hackam David J.
Published: June 2012

The fetal intestinal mucosa is characterized by elevated Toll-like receptor 4 (TLR4) expression, which can lead to the development of necrotizing enterocolitis (NEC)—a devastating inflammatory disease of the premature intestine—upon exposure to microbes. To define endogenous strategies that could reduce TLR4 signaling, we hypothesized that amniotic fluid can inhibit TLR4 signaling within the fetal intestine and attenuate experimental NEC, and we sought to determine the mechanisms involved. We show here that microinjection of amniotic fluid into the fetal (embryonic day 18.5) gastrointestinal tract reduced LPS-mediated signaling within the fetal intestinal mucosa. Amniotic fluid is abundant in EGF, which we show is required for its inhibitory effects on TLR4 signaling via peroxisome proliferator-activated receptor, because inhibition of EGF receptor (EGFR) with cetuximab or EGF-depleted amniotic fluid blocked the inhibitory effects of amniotic fluid on TLR4, whereas amniotic fluid did not prevent TLR4 signaling in EGFR- or peroxisome proliferator-activated receptor γ–deficient enterocytes or in mice deficient in intestinal epithelial EGFR, and purified EGF attenuated the exaggerated intestinal mucosal TLR4 signaling in wild-type mice. Moreover, amniotic fluid-mediated TLR4 inhibition reduced the severity of NEC in mice through EGFR activation. Strikingly, NEC development in both mice and humans was associated with reduced EGFR expression that was restored upon the administration of amniotic fluid in mice or recovery from NEC in humans, suggesting that a lack of amniotic fluid-mediated EGFR signaling could predispose to NEC. These findings may explain the unique susceptibility of premature infants to the development of NEC and offer therapeutic approaches to this devastating disease.
Younger Dryas cooling and the Greenland climate response to CO
2
Authors: Liu Zhengyu , Carlson Anders E. , He Feng , Brady Esther C. , Otto-Bliesner Bette L. , Briegleb Bruce P. , Wehrenberg Mark , Clark Peter U. , Wu Shu , Cheng Jun , Zhang Jiaxu , Noone David , Zhu Jiang
Published: June 2012

Greenland ice-core δ
18
O-temperature reconstructions suggest a dramatic cooling during the Younger Dryas (YD; 12.9–11.7 ka), with temperatures being as cold as the earlier Oldest Dryas (OD; 18.0–14.6 ka) despite an approximately 50 ppm rise in atmospheric CO
2
. Such YD cooling implies a muted Greenland climate response to atmospheric CO
2
, contrary to physical predictions of an enhanced high-latitude response to future increases in CO
2
. Here we show that North Atlantic sea surface temperature reconstructions as well as transient climate model simulations suggest that the YD over Greenland should be substantially warmer than the OD by approximately 5 °C in response to increased atmospheric CO
2
. Additional experiments with an isotope-enabled model suggest that the apparent YD temperature reconstruction derived from the ice-core δ
18
O record is likely an artifact of an altered temperature-δ
18
O relationship due to changing deglacial atmospheric circulation. Our results thus suggest that Greenland climate was warmer during the YD relative to the OD in response to rising atmospheric CO
2
, consistent with sea surface temperature reconstructions and physical predictions, and has a sensitivity approximately twice that found in climate models for current climate due to an enhanced albedo feedback during the last deglaciation.
Comparison of the H
+
/ATP ratios of the H
+
-ATP synthases from yeast and from chloroplast
Authors: Petersen Jan , Förster Kathrin , Turina Paola , Gräber Peter
Published: June 2012

F
0
F
1
-ATP synthases use the free energy derived from a transmembrane proton transport to synthesize ATP from ADP and inorganic phosphate. The number of protons translocated per ATP (H
+
/ATP ratio) is an important parameter for the mechanism of the enzyme and for energy transduction in cells. Current models of rotational catalysis predict that the H
+
/ATP ratio is identical to the stoichiometric ratio of c-subunits to β-subunits. We measured in parallel the H
+
/ATP ratios at equilibrium of purified F
0
F
1
s from yeast mitochondria (c/β = 3.3) and from spinach chloroplasts (c/β = 4.7). The isolated enzymes were reconstituted into liposomes and, after energization of the proteoliposomes with acid–base transitions, the initial rates of ATP synthesis and hydrolysis were measured as a function of ΔpH. The equilibrium ΔpH was obtained by interpolation, and from its dependency on the stoichiometric ratio, [ATP]/([ADP]·[P
i
]), finally the thermodynamic H
+
/ATP ratios were obtained: 2.9 ± 0.2 for the mitochondrial enzyme and 3.9 ± 0.3 for the chloroplast enzyme. The data show that the thermodynamic H
+
/ATP ratio depends on the stoichiometry of the c-subunit, although it is not identical to the c/β ratio.
Cholesterol-tethered platinum II-based supramolecular nanoparticle increases antitumor efficacy and reduces nephrotoxicity
Authors: Sengupta Poulomi , Basu Sudipta , Soni Shivani , Pandey Ambarish , Roy Bhaskar , Oh Michael S. , Chin Kenneth T. , Paraskar Abhimanyu S. , Sarangi Sasmit , Connor Yamicia , Sabbisetti Venkata S. , Kopparam Jawahar , Kulkarni Ashish , Muto Katherine , Amarasiriwardena Chitra , Jayawardene Innocent , Lupoli Nicola , Dinulescu Daniela M. , Bonventre Joseph V. , Mashelkar Raghunath A. , Sengupta Shiladitya
Published: June 2012

Nanoscale drug delivery vehicles have been harnessed extensively as carriers for cancer chemotherapeutics. However, traditional pharmaceutical approaches for nanoformulation have been a challenge with molecules that exhibit incompatible physicochemical properties, such as platinum-based chemotherapeutics. Here we propose a paradigm based on rational design of active molecules that facilitate supramolecular assembly in the nanoscale dimension. Using cisplatin as a template, we describe the synthesis of a unique platinum (II) tethered to a cholesterol backbone via a unique monocarboxylato and O→Pt coordination environment that facilitates nanoparticle assembly with a fixed ratio of phosphatidylcholine and 1,2-distearoyl-
sn
-glycero-3-phosphoethanolamine-
N
-[amino (polyethylene glycol)-2000]. The nanoparticles formed exhibit lower IC
50
values compared with carboplatin or cisplatin in vitro, and are active in cisplatin-resistant conditions. Additionally, the nanoparticles exhibit significantly enhanced in vivo antitumor efficacy in murine 4T1 breast cancer and in K-Ras
LSL/+
/Pten
fl/fl
ovarian cancer models with decreased systemic- and nephro-toxicity. Our results indicate that integrating rational drug design and supramolecular nanochemistry can emerge as a powerful strategy for drug development. Furthermore, given that platinum-based chemotherapeutics form the frontline therapy for a broad range of cancers, the increased efficacy and toxicity profile indicate the constructed nanostructure could translate into a next-generation platinum-based agent in the clinics.
Structural study on the architecture of the bacterial ATP synthase F
o
motor
Authors: Hakulinen Jonna K. , Klyszejko Adriana L. , Hoffmann Jan , Eckhardt-Strelau Luise , Brutschy Bernd , Vonck Janet , Meier Thomas
Published: June 2012

We purified the F
o
complex from the
Ilyobacter tartaricus
Na
+
-translocating F
1
F
o
-ATP synthase and performed a biochemical and structural study. Laser-induced liquid bead ion desorption MS analysis demonstrates that all three subunits of the isolated F
o
complex were present and in native stoichiometry (ab
2
c
11
). Cryoelectron microscopy of 2D crystals yielded a projection map at a resolution of 7.0 Å showing electron densities from the c
11
rotor ring and up to seven adjacent helices. A bundle of four helices belongs to the stator a-subunit and is in contact with c
11
. A fifth helix adjacent to the four-helix bundle interacts very closely with a c-subunit helix, which slightly shifts its position toward the ring center. Atomic force microscopy confirms the presence of the F
o
stator, and a height profile reveals that it protrudes less from the membrane than c
11
. The data limit the dimensions of the subunit a/c-ring interface: Three helices from the stator region are in contact with three c
11
helices. The location and distances of the stator helices impose spatial restrictions on the bacterial F
o
complex.
Ers1 links HP1 to RNAi
Authors: Rougemaille Mathieu , Braun Sigurd , Coyle Scott , Dumesic Phillip A. , Garcia Jennifer F. , Isaac Richard Stefan , Libri Domenico , Narlikar Geeta J. , Madhani Hiten D.
Published: June 2012

Pericentromeric heterochromatin formation is mediated by repressive histone H3 lysine 9 methylation (H3K9Me) and its recognition by HP1 proteins. Intriguingly, in many organisms, RNAi is coupled to this process through poorly understood mechanisms.
In Schizosaccharomyces pombe
, the H3-K9 methyltransferase Clr4 and the heterochromatin protein 1 (HP1) ortholog Swi6 are critical for RNAi, whereas RNAi stimulates H3K9Me. In addition to the endoribonuclease Dcr1, RNAi in
S. pombe
requires two interacting protein complexes, the RITS complex, which contains an Argonaute subunit, and the RDRC complex, which contains an RNA-dependent RNA polymerase subunit. We previously identified Ers1 (essential for RNAi-dependent silencing) as an orphan protein that genetically acts in the RNAi pathway. Using recombinant proteins, we show here that Ers1 directly and specifically interacts with HP1/Swi6. Two-hybrid assays indicate that Ers1 also directly interacts with several RNAi factors. Consistent with these interactions, Ers1 associates in vivo with the RITS complex, the RDRC complex, and Dcr1, and it promotes interactions between these factors. Ers1, like Swi6, is also required for RNAi complexes to associate with pericentromeric noncoding RNAs. Overexpression of Ers1 results in a dominant-negative phenotype that can be specifically suppressed by increasing levels of the RDRC subunit Hrr1 or of Dcr1, further supporting a functional role for Ers1 in promoting the assembly of the RNAi machinery. Through the interactions described here, Ers1 may promote RNAi by tethering the corresponding enzyme complexes to HP1-coated chromatin, thereby placing them in proximity to the nascent noncoding RNA substrate.
Heavy use of equations impedes communication among biologists
Authors: Fawcett Tim W. , Higginson Andrew D.
Published: June 2012

Most research in biology is empirical, yet empirical studies rely fundamentally on theoretical work for generating testable predictions and interpreting observations. Despite this interdependence, many empirical studies build largely on other empirical studies with little direct reference to relevant theory, suggesting a failure of communication that may hinder scientific progress. To investigate the extent of this problem, we analyzed how the use of mathematical equations affects the scientific impact of studies in ecology and evolution. The density of equations in an article has a significant negative impact on citation rates, with papers receiving 28% fewer citations overall for each additional equation per page in the main text. Long, equation-dense papers tend to be more frequently cited by other theoretical papers, but this increase is outweighed by a sharp drop in citations from nontheoretical papers (35% fewer citations for each additional equation per page in the main text). In contrast, equations presented in an accompanying appendix do not lessen a paper’s impact. Our analysis suggests possible strategies for enhancing the presentation of mathematical models to facilitate progress in disciplines that rely on the tight integration of theoretical and empirical work.
α-Helical element at the hormone-binding surface of the insulin receptor functions as a signaling element to activate its tyrosine kinase
Authors: Whittaker Jonathan , Whittaker Linda J. , Roberts Charles T. , Phillips Nelson B. , Ismail-Beigi Faramarz , Lawrence Michael C. , Weiss Michael A.
Published: June 2012

The primary hormone-binding surface of the insulin receptor spans one face of the N-terminal β-helix of the α-subunit (the L1 domain) and an α-helix in its C-terminal segment (αCT). Crystallographic analysis of the free ectodomain has defined a contiguous dimer-related motif in which the αCT α-helix packs against L1 β-strands 2 and 3. To relate structure to function, we exploited expanded genetic-code technology to insert photo-activatable probes at key sites in L1 and αCT. The pattern of αCT-mediated photo–cross-linking within the free and bound receptor is in accord with the crystal structure and prior mutagenesis. Surprisingly, L1 photo-probes in β-strands 2 and 3, predicted to be shielded by αCT, efficiently cross-link to insulin. Furthermore, anomalous mutations were identified on neighboring surfaces of αCT and insulin that impair hormone-dependent activation of the intracellular receptor tyrosine kinase (contained within the transmembrane β-subunit) disproportionately to their effects on insulin binding. Taken together, these results suggest that αCT, in addition to its hormone-recognition role, provides a signaling element in the mechanism of receptor activation.
p38γ and p38δ kinases regulate the Toll-like receptor 4 (TLR4)-induced cytokine production by controlling ERK1/2 protein kinase pathway activation
Authors: Risco Ana , del Fresno Carlos , Mambol Agnes , Alsina-Beauchamp Dayanira , MacKenzie Kirsty F. , Yang Huei-Ting , Barber Domingo F. , Morcelle Carmen , Arthur J. Simon C. , Ley Steven C. , Ardavin Carlos , Cuenda Ana
Published: June 2012

On the basis mainly of pharmacological experiments, the p38α MAP kinase isoform has been established as an important regulator of immune and inflammatory responses. However, the role of the related p38γ and p38δ kinases has remained unclear. Here, we show that deletion of p38γ and p38δ impaired the innate immune response to lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand, by blocking the extracellular signal-regulated kinase 1/2 (ERK1/2) activation in macrophages and dendritic cells. p38γ and p38δ were necessary to maintain steady-state levels of tumor progression locus 2 (TPL2), the MKK kinase that mediates ERK1/2 activation after TLR4 stimulation. TNFα, IL-1β, and IL-10 production were reduced in LPS-stimulated macrophages from p38γ/δ-null mice, whereas IL-12 and IFNβ production increased, in accordance with the known effects of TPL2/ERK1/2 signaling on the induction of these cytokines. Furthermore, p38γ/δ-deficient mice were less sensitive than controls to LPS-induced septic shock, showing lower TNFα and IL-1β levels after challenge. Together, our results establish p38γ and p38δ as key components in innate immune responses.
Structural evidence of a new catalytic intermediate in the pathway of ATP hydrolysis by F
1
–ATPase from bovine heart mitochondria
Authors: Rees David M. , Montgomery Martin G. , Leslie Andrew G. W. , Walker John E.
Published: June 2012

The molecular description of the mechanism of F
1
–ATPase is based mainly on high-resolution structures of the enzyme from mitochondria, coupled with direct observations of rotation in bacterial enzymes. During hydrolysis of ATP, the rotor turns counterclockwise (as viewed from the membrane domain of the intact enzyme) in 120° steps. Because the rotor is asymmetric, at any moment the three catalytic sites are at different points in the catalytic cycle. In a “ground-state” structure of the bovine enzyme, one site (β
E
) is devoid of nucleotide and represents a state that has released the products of ATP hydrolysis. A second site (β
TP
) has bound the substrate, magnesium. ATP, in a precatalytic state, and in the third site (β
DP
), the substrate is about to undergo hydrolysis. Three successive 120° turns of the rotor interconvert the sites through these three states, hydrolyzing three ATP molecules, releasing the products and leaving the enzyme with two bound nucleotides. A transition-state analog structure, F
1
–TS, displays intermediate states between those observed in the ground state. For example, in the β
DP
-site of F
1
–TS, the terminal phosphate of an ATP molecule is undergoing in-line nucleophilic attack by a water molecule. As described here, we have captured another intermediate in the catalytic cycle, which helps to define the order of substrate release. In this structure, the β
E
-site is occupied by the product ADP, but without a magnesium ion or phosphate, providing evidence that the nucleotide is the last of the products of ATP hydrolysis to be released.
Galactose repressor mediated intersegmental chromosomal connections in
Escherichia coli
Authors: Qian Zhong , Dimitriadis Emilios K. , Edgar Rotem , Eswaramoorthy Prahathees , Adhya Sankar
Published: June 2012

By microscopic analysis of fluorescent-labeled GalR, a regulon-specific transcription factor in
Escherichia coli
, we observed that GalR is present in the cell as aggregates (one to three fluorescent foci per cell) in nongrowing cells. To investigate whether these foci represent GalR-mediated association of some of the GalR specific DNA binding sites (
gal
operators), we used the chromosome conformation capture (3C) method in vivo. Our 3C data demonstrate that, in stationary phase cells, many of the operators distributed around the chromosome are interacted. By the use of atomic force microscopy, we showed that the observed remote chromosomal interconnections occur by direct interactions between DNA-bound GalR not involving any other factors. Mini plasmid DNA circles with three or five operators positioned at defined loci showed GalR-dependent loops of expected sizes of the intervening DNA segments. Our findings provide unique evidence that a transcription factor participates in organizing the chromosome in a three-dimensional structure. We believe that these chromosomal connections increase local concentration of GalR for coordinating the regulation of widely separated target genes, and organize the chromosome structure in space, thereby likely contributing to chromosome compaction.
Acute augmentation of epoxygenated fatty acid levels rapidly reduces pain-related behavior in a rat model of type I diabetes
Authors: Inceoglu Bora , Wagner Karen M. , Yang Jun , Bettaieb Ahmed , Schebb Nils H. , Hwang Sung Hee , Morisseau Christophe , Haj Fawaz G. , Hammock Bruce D.
Published: June 2012

The nerve damage occurring as a consequence of glucose toxicity in diabetes leads to neuropathic pain, among other problems. This pain dramatically reduces the quality of life in afflicted patients. The progressive damage to the peripheral nervous system is irreversible although strict control of hyperglycemia may prevent further damage. Current treatments include tricyclic antidepressants, anticonvulsants, and opioids, depending on the severity of the pain state. However, available therapeutics have drawbacks, arguing for the need to better understand the pathophysiology of neuropathic pain and develop novel treatments. Here we demonstrate that stabilization of a class of bioactive lipids, epoxygenated fatty acids (EpFAs), greatly reduces allodynia in rats caused by streptozocin-induced type I diabetes. Inhibitors of the soluble epoxide hydrolase (sEHI) elevated and stabilized the levels of plasma and spinal EpFAs, respectively, and generated dose-dependent antiallodynic effects more potently and efficaciously than gabapentin. In acute experiments, positive modulation of EpFAs did not display differences in insulin sensitivity, glucose tolerance, or insulin secretion, indicating the efficacy of sEHIs are not related to the glycemic status. Quantitative metabolomic analysis of a panel of 26 bioactive lipids demonstrated that sEHI-mediated antiallodynic effects coincided with a selective elevation of the levels of EpFAs in the plasma, and a decrease in degradation products coincided with the dihydroxy fatty acids in the spinal cord. Overall, these results argue that further efforts in understanding the spectrum of effects of EpFAs will yield novel opportunities in treating neuropathic pain.
On-chip manipulation of single microparticles, cells, and organisms using surface acoustic waves
Authors: Ding Xiaoyun , Lin Sz-Chin Steven , Kiraly Brian , Yue Hongjun , Li Sixing , Chiang I-Kao , Shi Jinjie , Benkovic Stephen J. , Huang Tony Jun
Published: June 2012

Techniques that can dexterously manipulate single particles, cells, and organisms are invaluable for many applications in biology, chemistry, engineering, and physics. Here, we demonstrate standing surface acoustic wave based “acoustic tweezers” that can trap and manipulate single microparticles, cells, and entire organisms (i.e.,
Caenorhabditis elegans
) in a single-layer microfluidic chip. Our acoustic tweezers utilize the wide resonance band of chirped interdigital transducers to achieve real-time control of a standing surface acoustic wave field, which enables flexible manipulation of most known microparticles. The power density required by our acoustic device is significantly lower than its optical counterparts (10,000,000 times less than optical tweezers and 100 times less than optoelectronic tweezers), which renders the technique more biocompatible and amenable to miniaturization. Cell-viability tests were conducted to verify the tweezers’ compatibility with biological objects. With its advantages in biocompatibility, miniaturization, and versatility, the acoustic tweezers presented here will become a powerful tool for many disciplines of science and engineering.
Widespread dynamic DNA methylation in response to biotic stress
Authors: Dowen Robert H. , Pelizzola Mattia , Schmitz Robert J. , Lister Ryan , Dowen Jill M. , Nery Joseph R. , Dixon Jack E. , Ecker Joseph R.
Published: June 2012

Regulation of gene expression by DNA methylation is crucial for defining cellular identities and coordinating organism-wide developmental programs in many organisms. In plants, modulation of DNA methylation in response to environmental conditions represents a potentially robust mechanism to regulate gene expression networks; however, examples of dynamic DNA methylation are largely limited to gene imprinting. Here we report an unexpected role for DNA methylation in regulation of the
Arabidopsis thaliana
immune system. Profiling the DNA methylomes of plants exposed to bacterial pathogen, avirulent bacteria, or salicylic acid (SA) hormone revealed numerous stress-induced differentially methylated regions, many of which were intimately associated with differentially expressed genes. In response to SA, transposon-associated differentially methylated regions, which were accompanied by up-regulation of 21-nt siRNAs, were often coupled to transcriptional changes of the transposon and/or the proximal gene. Thus, dynamic DNA methylation changes within repetitive sequences or transposons can regulate neighboring genes in response to SA stress.
Migrations of Common Snook from a Tidal River with Implications for Skipped Spawning
Authors: Trotter Alexis A. , Blewett David A. , Taylor Ronald G. , Stevens Philip W.
Published: June 2012

Common snook Centropomus undecimalis support a recreational fishery that contributes greatly to Florida's economy and have been the subject of many diverse studies in which aspects of their life history, reproductive biology, and fishery dynamics have been defined. The current stock assessment contains assumptions based on historical reproductive schedules measured at the population level during the early 1990s. Recent research, however, suggests our understanding of habitat residency and spawning schedules may be overly generalized. We used acoustic telemetry to study the movements and migrations of common snook from the tidal reaches of the Caloosahatchee River, a major tributary of Charlotte Harbor, for 3 years (2005–2007). During this period, 60% of the tagged snook left the study area during at least one spawning season, presumably to enter higher salinity waters where they spawn. The onset and duration of these annual migrations are similar to those reported in previous reproductive studies of snook, but individual dynamics varied. Unexpectedly, 40% of tagged snook remained within the monitored portion of the river for up to three spawning seasons, providing initial evidence for skipped spawning. These detailed data indicate differential individual contributions to total spawning biomass. If further investigation confirms skipped spawning in common snook and shows similar rates of skipped reproduction throughout the snook population, this information should be incorporated into future stock assessments.
Spring and Summer Distribution and Habitat Use by Adult Threatened Spotted Gar in Rondeau Bay, Ontario, Using Radiotelemetry
Authors: Glass W. R. , Corkum L. D. , Mandrak N. E.
Published: June 2012

The spotted gar Lepisosteus oculatus is designated as threatened in Canada under the federal Species at Risk Act. Identification and protection of critical habitat is an important component of recovering species at risk. To understand the habitat utilization of the adult life stage of the spotted gar in Rondeau Bay, a shallow coastal wetland of Lake Erie, external radio transmitters were surgically attached to 37 specimens in May 2007. These individuals were tracked at 224 discrete locations throughout the spring and summer of 2007. Aquatic macrophytes were present at 201 (90%) of these sites. Habitat and water chemistry data were collected at all tracked locations occupied by spotted gars. On the basis of electivity indices, in spring spotted gars showed a strong preference for shallow (<0.5‐m) and deep (>2.5‐m) waters with pH values <8.5. In summer, strong preference was shown for areas with mixed macrophyte beds. Spotted gars were found to relate to specific depths and cover rather than to shoreline features in Rondeau Bay. The study results are being used by the spotted gar Recovery Team to identify critical habitat in Rondeau Bay. This critical habitat designation will be used to ensure the protection of habitat needed to preserve the species in Canada, in part by curtailing the removal of aquatic vegetation in Rondeau Bay.
A Collaborative Approach to Teaching Medical Students how to Screen, Intervene, and Treat Substance Use Disorders
Authors: Neufeld Karin J. , Alvanzo Anika , King Van L. , Feldman Leonard , Hsu Jeffrey H. , Rastegar Darius A. , Colbert Jorie M. , MacKinnon Dean F.
Published: June 2012

Few medical schools require a stand-alone course to develop knowledge and skills relevant to substance use disorders (SUDs). The authors successfully initiated a new course for second-year medical students that used screening, brief intervention, and referral to treatment (SBIRT) as the course foundation. The 15-hour course (39 faculty teaching hours) arose from collaboration between faculty in Departments of Medicine and Psychiatry and included 5 hours of direct patient interaction during clinical demonstrations and in small-group skills development. Pre- and post-exam results suggest that the course had a significant impact on knowledge about SUDs. The authors’ experience demonstrates that collaboration between 2 clinical departments can produce a successful second-year medical student course based in SBIRT principles.
Pennsylvania SBIRT Medical and Residency Training: Developing, Implementing, and Evaluating an Evidenced-Based Program
Authors: Pringle Janice L. , Melczak Michael , Johnjulio William , Campopiano Melinda , Gordon Adam J. , Costlow Monica
Published: June 2012

Medical residents do not receive adequate training in screening, brief intervention, and referral to treatment (SBIRT) for alcohol and other drug use disorders. The federally funded Pennsylvania SBIRT Medical and Residency Training program (SMaRT) is an evidence-based curriculum with goals of training residents in SBIRT knowledge and skills and disseminating the curriculum throughout the medical residency programs. The SMaRT program collaborates with 4 hospital systems and 7 residency sites, with a target of 1147 residents to be trained. This brief report describes the design of the SMaRT program curriculum, implementation across settings and programs, and its evaluation methods.
Using Standardized Patients to Evaluate Screening, Brief Intervention, and Referral to Treatment (SBIRT) Knowledge and Skill Acquisition for Internal Medicine Residents
Authors: Satterfield Jason M. , O'Sullivan Patricia , Satre Derek D. , Tsoh Janice Y. , Batki Steven L. , Julian Kathy , McCance-Katz Elinore F. , Wamsley Maria
Published: June 2012

Comprehensive clinical competency curricula for hazardous drinking and substance use disorders (SUDs) exists for medical students, residents, and practicing health care providers. Evaluations of these curricula typically focus on learner attitudes and knowledge, although changes in clinical skills are of greater interest and utility. The authors present a pre-post clinical skill evaluation of a 10-hour screening, brief intervention, and referral to treatment (SBIRT) curriculum for hazardous drinking and SUDs for primary care internal medicine residents using standardized patient examinations to better determine the impact of SBIRT training on clinical practice. Residents had large improvements in history taking, substance use screening skills, SUD assessment and diagnostic skills, and in SBIRT knowledge, including documentation, systems, and diversity issues. Residents made moderate improvements in brief intervention skills. Future SBIRT curricular evaluations would ideally include a controlled comparison with larger samples from multiple institutions.
Institutional Incorporation of Screening, Brief Intervention, and Referral to Treatment (SBIRT) in Residency Training: Achieving a Sustainable Curriculum
Authors: Scott Denise M. , McLaurin-Jones TyWanda , Brown Fannie D. , Newton Robin , Marshall Vanessa J. , Kalu Nnenna , Cain Gloria E. , Taylor Robert E.
Published: June 2012

The success of implementing a screening, brief intervention and referral to treatment (SBIRT) program within a medical residency program for sustainability is contingent upon a well-crafted training curriculum that incorporates substance abuse education and clinical practice skills. The goal of the Howard University (HU) SBIRT program is to train residents in providing culturally competent evidence-based screening, brief intervention and referral to treatment for patients who have a substance use disorder or who are at risk for developing the disorder. Utilizing the Office of Graduate Medical Education (GME) allows all residents to be trained in SBIRT techniques and receive continuing education in SBIRT and SBIRT-related topics through new resident orientation and the core lecture series. The utilization of Graduate Medical Education office has allowed a robust SBIRT training program to be implemented into medical residency education, contributing to the sustainability of SBIRT as a component of patient care.
Implementation of a “Learner-Driven” Curriculum: An Screening, Brief Intervention, and Referral to Treatment (SBIRT) Interdisciplinary Primary Care Model
Authors: Stanton Marina R. , Atherton W. Leigh , Toriello Paul J. , Hodgson Jennifer L.
Published: June 2012

Although screening, brief intervention, and referral to treatment (SBIRT) has been a popular model to address potential substance abuse issues in primary care, there is a need for innovative approaches for training providers and staff on SBIRT protocols. An interdisciplinary approach to SBIRT training, named ICARE, was implemented at 3 different medical settings. The ICARE team trained 85 employees at an academic family medicine residency center and 37 employees across 2 rural community health care clinics. Using an innovative “learner-driven” approach, the authors implemented a combination of didactic and interactive training strategies that included on-site coaching, patient simulation exercises, as well as large- and small-group learning.
Skills-Based Residency Training in Alcohol Screening and Brief Intervention: Results from the Georgia-Texas “Improving Brief Intervention” Project
Authors: Seale J. Paul , Velasquez Mary M. , Johnson J. Aaron , Shellenberger Sylvia , von Sternberg Kirk , Dodrill Carrie , Boltri John M. , Takei Roy , Clark Denice , Grace Daniel
Published: June 2012

Alcohol screening and brief intervention (SBI) is recommended for all primary care patients but is underutilized. This project trained 111 residents and faculty in 8 family medicine residencies to conduct SBI and implement SBI protocols in residency clinics, then assessed changes in self-reported importance and confidence in performing SBI and brief intervention (BI) rates. Clinicians reported significant increases in role security, confidence, and ability to help drinkers reduce drinking and decreased importance of factors that might dissuade them from performing SBI. Stage of change measures indicated 37% of clinicians progressed toward action or maintenance in performing SBI; however, numbers of reported BIs did not increase. At all time points, 33% to 36% of clinicians reported BIs with ≥10% of the last 50 patients. Future studies should focus on increasing intervention rates using more patient-centered BI approaches, quality improvement approaches, and systems changes that could increase opportunities for performing BIs.
Temperature Affects Growth and Tissue Fatty Acid Composition of Juvenile Atlantic Spadefish
Authors: Trushenski Jesse T , Schwarz Michael H , Bowzer John C , Gause Brian R , Fenn Teresa , Delbos Brendan C
Published: June 2012

The Atlantic spadefish Chaetodipterus faber holds potential as an aquaculture species, but successful intensive production of this species will depend on the identification of proper husbandry methods, including the use of optimal water temperatures. Accordingly, we evaluated the growth performance and tissue composition of juveniles (37.8 ± 0.5 g [mean ± SE]) reared at 20, 25, or 30°C in indoor recirculation systems (three 100-L tanks per temperature, five fish per tank) for 8 weeks. Weight gain, specific growth rate, feed conversion ratio, and feed intake were significantly affected by water temperature, and increasing temperature yielded greater feed intake and growth rates as well as lower feed conversion values. Although performance observed at 25°C was statistically similar, growth and growth efficiency were nonetheless marginally superior within the 30°C treatment group. Fish exhibited differences in the fatty acid composition of neutral and polar lipid fractions of gill and muscle tissue that were broadly consistent with homeoviscous adaptation to cooler or warmer water temperatures; specifically, increasing proportions of unsaturated and longer-chain fatty acids were observed in fish from cooler water temperatures. This suggests that unsaturates, particularly long-chain polyunsaturated fatty acids that are associated with maximum membrane fluidity at cold temperatures, are critical in the diet of Atlantic spadefish depending on culture conditions.
Message from the Editor
Authors: Thomas Paul
Published: June 2012

Due to a processing error, this article was omitted from the printed copy of volume 52, issue 4 of Nuclear Fusion. The missing editorial is as follows:

Whilst travelling to Vienna to hand over the Editorship of Nuclear Fusion to Ron Stambaugh, I jotted down a few ideas to put in a farewell message. Somewhat unsurprisingly, I find them almost identical to the remarks that Chris Schueller made in handing over to me five years ago. Both of us served in this role for five years, which seems like a good timescale to replace presidents and editors alike; just to allow a fresh approach. In addition, since I have been directly involved in ITER, I have found it increasingly difficult, due to time pressure, to give the journal the attention that it deserves. Therefore, I am very pleased that Ron Stambaugh has agreed to take over as Editor. Not only does he bring the experience as a leading figure in the US fusion programme but, in addition, he has all the contacts, worldwide, from his leadership of the ITPA. I am completely assured that the journal is in a highly competent pair of hands.

Such a farewell should not lack my heartfelt thanks to all of those who have made being Editor of Nuclear Fusion so enjoyable and stimulating; readership, authors, referees, the Editorial Board and the NF Office alike. I wish Ron all the best for his tenure and have offered such help and support as I am able to give.
On the Lebesgue decomposition of positive linear functionals
Authors: Szũcs Zsolt
Published: June 2012

In this paper we will prove that the Lebesgue decomposition of positive linear functionals on Banach

∗

^*

-algebras corresponds with the Lebesgue decomposition of the nonnegative forms derived from the functionals.
Transient anomalous sub-diffusion on bounded domains
Authors: Meerschaert Mark , Nane Erkan , Vellaisamy P.
Published: June 2012

This paper develops strong solutions and stochastic solutions for the tempered fractional diffusion equation on bounded domains. First the eigenvalue problem for tempered fractional derivatives is solved. Then a separation of variables and eigenfunction expansions in time and space are used to write strong solutions. Finally, stochastic solutions are written in terms of an inverse subordinator.
Sharp ill-posedness and well-posedness results for the KdV-Burgers equation: The periodic case
Authors: Molinet Luc , Vento Stéphane
Published: June 2012

We prove that the KdV-Burgers equation is globally well-posed in

H

−
1

(

T

)

H^{-1}(\mathbb {T})

with a solution-map that is analytic from

H

−
1

(

T

)

H^{-1}(\mathbb {T})

to

C
(
[
0
,
T
]
;

H

−
1

(

T

)
)

C([0,T];H^{-1}(\mathbb {T}))

, whereas it is ill-posed in

H
s

(

T

)

H^s(\mathbb {T})

, as soon as

s
>
−
1

s>-1

, in the sense that the flow-map

u
0

↦
u
(
t
)

u_0\mapsto u(t)

cannot be continuous from

H
s

(

T

)

H^s(\mathbb {T})

to even

D

′

(

T

)

{\mathcal D}’(\mathbb {T})

at any fixed

t
>
0

t>0

small enough. In view of the result of Kappeler and Topalov for KdV it thus appears that even if the dissipation part of the KdV-Burgers equation allows us to lower the

C
∞

C^\infty

critical index with respect to the KdV equation, it does not permit us to improve the

C
0

C^0

critical index.
The Medusa algorithm for polynomial matings
Authors: Boyd Suzanne , Henriksen Christian
Published: June 2012

The Medusa algorithm takes as input two postcritically finite quadratic polynomials and outputs the quadratic rational map which is the mating of the two polynomials (if it exists). Specifically, the output is a sequence of approximations for the parameters of the rational map, as well as an image of its Julia set. Whether these approximations converge is answered using Thurston’s topological characterization of rational maps.

This algorithm was designed by John Hamal Hubbard, and implemented in 1998 by Christian Henriksen and REU students David Farris and Kuon Ju Liu.

In this paper we describe the algorithm and its implementation, discuss some output from the program (including many pictures) and related questions. Specifically, we include images and a discussion for some shared matings, Lattès examples, and tuning sequences of matings.
Advances in Research on Phytophthora capsici on Vegetable Crops in The United States
Authors: Granke Leah L. , Quesada-Ocampo Lina , Lamour Kurt , Hausbeck Mary K.
Published: June 2012

Since L. H. Leonian's first description of Phytophthora capsici as a pathogen of chile pepper in 1922, we have made many advances in our understanding of this pathogen's biology, host range, dissemination, and management. P. capsici causes foliar blighting, damping-off, wilting, and root, stem, and fruit rot of susceptible hosts, and economic losses are experienced annually in vegetable crops including cucurbits and peppers. Symptoms of P. capsici infection may manifest as stunting, girdling, or cankers for some cultivars or crops that are less susceptible. P. capsici continues to be a constraint on production, and implementation of an aggressive integrated management scheme can still result in insufficient control when weather is favorable for disease. Management of diseases caused by P. capsici is currently limited by the long-term survival of the pathogen as oospores in the soil, a wide host range, long-distance movement of the pathogen in surface water used for irrigation, the presence of fungicide-resistant pathogen populations, and a lack of commercially acceptable resistant host varieties. P. capsici can infect a wide range of hosts under laboratory and greenhouse conditions including cultivated crops, ornamentals, and native plants belonging to diverse plant families. As our understanding of P. capsici continues to grow, future research should focus on developing novel and effective solutions to manage this pathogen and prevent economic losses due to the diseases it causes.
Genetic Variation in Puccinia graminis Collected from Oats, Rye, and Barberry
Authors: Berlin Anna , Djurle Annika , Samils Berit , Yuen Jonathan
Published: June 2012

Puccinia graminis, the causal agent of stem rust, was collected from its alternate host barberry (Berberis spp.) and two different uredinial hosts, oats (Avena sativa) and rye (Secale cereale). The samples were analyzed using 11 polymorphic simple sequence repeat (SSR) markers. There were large differences between fungal populations on oats (P. graminis f. sp. avenae) and rye (P. graminis f. sp. secalis), and the genetic variation within the different formae speciales was also high. It was possible to distinguish between the two formae speciales on barberry. Additional genotypic groups not present in the field samples from oats and rye were also identified on barberry. Our results confirm the importance of barberry in maintaining the populations of P. graminis in Sweden and the importance of the sexual stage for the survival of the pathogen.