bluuebunny/crossref_metadata_2025 huggingface dataset:
Photodissociation of pyrrole-ammonia clusters below 218 nm: Quenching of statistical decomposition pathways under clustering conditions
Authors: Rodríguez J. D. , González M. G. , Rubio-Lago L. , Bañares L.
Published: September 2012

The excited state hydrogen transfer (ESHT) reaction in pyrrole-ammonia clusters (PyH·(NH3)n, n = 2–5) at excitation wavelengths below 218 nm down to 199 nm, has been studied using a combination of velocity map imaging and non-resonant detection of the NH4(NH3)n−1 products. Special care has been taken to avoid evaporation of solvent molecules from the excited clusters by controlling the intensity of both the excitation and probing lasers. The high resolution translational energy distributions obtained are analyzed on the base of an impulsive mechanism for the hydrogen transfer, which mimics the direct N−H bond dissociation of the bare pyrrole. In spite of the low dissociation wavelengths attained (∼200 nm) no evidence of hydrogen-loss statistical dynamics has been observed. The effects of clustering of pyrrole with ammonia molecules on the possible statistical decomposition channels of the bare pyrrole are discussed.
On the minimum coupling required for maximum theoretical power capture from vibration energy harvesters
Authors: Kim D. , Hewa-Kasakarage N. N. , Yoon S. , Hall N. A.
Published: September 2012

The minimum transducer coupling to enable maximum theoretical power capture from vibration energy harvesters is derived, leading to the simple conclusion that the product of the transducer coupling coefficient and resonance quality factor must be greater than two. Maximum theoretical power capture is experimentally demonstrated on a micromachined piezoelectric energy harvester comprised of a 20 μm thick epitaxial silicon cantilever with 800 nm thick lead-zirconate-titanate along the top surface and a bulk silicon mass at the tip. The coupling of these structures, although small (κ2=0.0033), is entirely sufficient to enable maximum theoretical power capture owing to light damping (Q=906).
The dingo and biodiversity conservation: response to Fleming et al. (2012)
Authors: Johnson Chris N. , Ritchie Euan G.
Published: August 2012

Several authors have recently argued that dingoes could be used to help conserve biodiversity in Australia. Fleming et al. (2012) [Australian Mammalogy 34, 119–131] offer the alternative view that restoration of dingo predation is unlikely to help native species, and is more likely to do harm. We think many of the arguments used by Fleming et al. to reach that conclusion are either unsound or beside the point, and we explain why.
A rock-ramp fishway expands nursery grounds of the endangered Macquarie perch (Macquaria australasica)
Authors: Broadhurst B. T. , Ebner B. C. , Clear R. C.
Published: August 2012

Prior to installation of a fishway at a road crossing in 2001, a remnant population of endangered Macquarie perch (Macquaria australasica) was confined to a 6-km section of the Cotter River, Australian Capital Territory. The purpose of the fishway was to provide passage past a barrier and to increase the extent of spawning grounds for M. australasica to an additional 22 km of river. The aim of the current study was to quantify the extent of nursery grounds of M. australasica in the Cotter River catchment by developing and applying a rapid, non-destructive technique for surveying juvenile M. australasica. From October to January in 2006–07 and 2007–08, pools were surveyed by snorkelling in the lower Cotter River to detect juvenile and larval M. australasica. The 9-km study reach consisted of the four pools immediately upstream of Cotter Reservoir, seven pools further upstream but still downstream of the rockramp fishway and 14 pools upstream of the fishway. In 2006–07, juvenile M. australasica were detected at 22 of 25 pools, including 13 of 14 pools upstream of the fishway. In spring/summer 2007–08, low visibility conditions frequently occurred throughout the river preventing survey on several occasions. However, recruitment of M. australasica was again detected upstream of the fishway. The increased extent of the nursery grounds of this M. australasica population has proven to be timely as an enlargement of the Cotter Reservoir, due for completion in 2012, will inundate more than 90% of prefishway nursery grounds in the Cotter River. Our study has demonstrated the benefit of installing a fishway in expanding the nursery grounds and the number of recruits of a remnant population of the endangered M. australasica. We also demonstrate the benefits of employing a visual survey technique to quantify the extent of the riverine nursery grounds of a fish population.
Vitamin D accelerates resolution of inflammatory responses during tuberculosis treatment
Authors: Coussens Anna K. , Wilkinson Robert J. , Hanifa Yasmeen , Nikolayevskyy Vladyslav , Elkington Paul T. , Islam Kamrul , Timms Peter M. , Venton Timothy R. , Bothamley Graham H. , Packe Geoffrey E. , Darmalingam Mathina , Davidson Robert N. , Milburn Heather J. , Baker Lucy V. , Barker Richard D. , Mein Charles A. , Bhaw-Rosun Leena , Nuamah Rosamond , Young Douglas B. , Drobniewski Francis A. , Griffiths Christopher J. , Martineau Adrian R.
Published: September 2012

Calcidiol, the major circulating metabolite of vitamin D, supports induction of pleiotropic antimicrobial responses in vitro. Vitamin D supplementation elevates circulating calcidiol concentrations, and thus has a potential role in the prevention and treatment of infection. The immunomodulatory effects of administering vitamin D to humans with an infectious disease have not previously been reported. To characterize these effects, we conducted a detailed longitudinal study of circulating and antigen-stimulated immune responses in ninety-five patients receiving antimicrobial therapy for pulmonary tuberculosis who were randomized to receive adjunctive high-dose vitamin D or placebo in a clinical trial, and who fulfilled criteria for per-protocol analysis. Vitamin D supplementation accelerated sputum smear conversion and enhanced treatment-induced resolution of lymphopaenia, monocytosis, hypercytokinaemia, and hyperchemokinaemia. Administration of vitamin D also suppressed antigen-stimulated proinflammatory cytokine responses, but attenuated the suppressive effect of antimicrobial therapy on antigen-stimulated secretion of IL-4, CC chemokine ligand 5, and IFN-α. We demonstrate a previously unappreciated role for vitamin D supplementation in accelerating resolution of inflammatory responses during tuberculosis treatment. Our findings suggest a potential role for adjunctive vitamin D supplementation in the treatment of pulmonary infections to accelerate resolution of inflammatory responses associated with increased risk of mortality.
Deficiency in TNFRSF13B (TACI) expands T-follicular helper and germinal center B cells via increased ICOS-ligand expression but impairs plasma cell survival
Authors: Ou Xijun , Xu Shengli , Lam Kong-Peng
Published: September 2012

Mutations in TNFRSF13B, better known as transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), contribute to common variable immunodeficiency and autoimmunity in humans. How TACI regulates these two opposing conditions is unclear, however. TACI binds the cytokines BAFF and APRIL, and previous studies using gene KO mice indicated that loss of TACI affected only T-cell–independent antibody responses. Here we demonstrate thatTaci−/−mice have expanded populations of T follicular helper (Tfh) and germinal center (GC) B cells in their spleens when immunized with T-cell–dependent antigen. The increased numbers of Tfhand GC B cells inTaci−/−mice are largely a result of up-regulation of inducible costimulator (ICOS) ligand on TACI-deficient B cells, given that ablation of one copy of theIcoslallele restores normal levels of Tfhand GC B cells inTaci−/−mice. Interestingly, despite the presence of increased Tfhand antigen-specific B cells, immunizedTaci−/−mice demonstrate defective antigen-specific antibody responses resulting from significantly reduced numbers of antibody-secreting cells (ASCs). This effect is attributed to the failure to down-regulate the proapoptotic molecule BIM inTaci−/−plasma cells. Ablation of BIM could rescue ASC formation inTaci−/−mice, suggesting that TACI is more important for the survival of plasma cells than for the differentiation of these cells. Thus, our data reveal dual roles for TACI in B-cell terminal differentiation. On one hand, TACI modulates ICOS ligand expression and thereby limits the size of Tfhand GC B-cell compartments and prevents autoimmunity. On the other hand, it regulates the survival of ASCs and plays an important role in humoral immunity.
In vivo reprogramming of Sox9
+
cells in the liver to insulin-secreting ducts
Authors: Banga Anannya , Akinci Ersin , Greder Lucas V. , Dutton James R. , Slack Jonathan M. W.
Published: September 2012

In embryonic development, the pancreas and liver share developmental history up to the stage of bud formation. Therefore, we postulated that direct reprogramming of liver to pancreatic cells can occur when suitable transcription factors are overexpressed. Using a polycistronic vector we misexpress
Pdx1
,
Ngn3
, and
MafA
in the livers of NOD-SCID mice rendered diabetic by treatment with streptozotocin (STZ). The diabetes is relieved long term. Many ectopic duct-like structures appear that express a variety of β-cell markers, including dense core granules visible by electron microscopy (EM). Use of a vector also expressing GFP shows that the ducts persist long after the viral gene expression has ceased, indicating that this is a true irreversible cell reprogramming event. We have recovered the insulin
+
cells by cell sorting and shown that they display glucose-sensitive insulin secretion. The early formed insulin
+
cells can be seen to coexpress SOX9 and are also labeled in mice lineage labeled for
Sox9
expression. SOX9
+
cells are normally found associated with small bile ducts in the periportal region, indicating that the duct-like structures arise from this source. This work confirms that developmentally related cells can be reprogrammed by suitable transcription factors and also suggests a unique therapy for diabetes.
Resistance of AustralianHelicoverpa armigerato fenvalerate is due to the chimeric P450 enzyme CYP337B3
Authors: Joußen Nicole , Agnolet Sara , Lorenz Sybille , Schöne Sebastian E. , Ellinger Renate , Schneider Bernd , Heckel David G.
Published: September 2012

Worldwide, increasing numbers of insects have evolved resistance to a wide range of pesticides, which hampers their control in the field and, therefore, threatens agriculture. Members of the carboxylesterase and cytochrome P450 monooxygenase superfamilies are prominent candidates to confer metabolic resistance to pyrethroid insecticides. Both carboxylesterases and P450 enzymes have been shown to be involved in pyrethroid resistance in AustralianHelicoverpa armigera, the noctuid species possessing by far the most reported resistance cases worldwide. However, specific enzymes responsible for pyrethroid resistance in field populations of this species have not yet been identified. Here, we show that the resistance toward fenvalerate in an Australian strain ofH. armigerais due to a unique P450 enzyme, CYP337B3, which arose from unequal crossing-over between two parental P450 genes, resulting in a chimeric enzyme. CYP337B3 is capable of metabolizing fenvalerate into 4′-hydroxyfenvalerate, which exhibits no toxic effect on susceptible larvae; enzymes from the parental P450 genes showed no detectable fenvalerate metabolism. Furthermore, a polymorphicH. armigerastrain could be bred into a susceptible line possessing the parental genesCYP337B1andCYP337B2and a resistant line possessing onlyCYP337B3. The exclusive presence ofCYP337B3in resistant insects of this strain confers a 42-fold resistance to fenvalerate. Thus, in addition to previously documented genetic mechanisms of resistance, recombination can also generate selectively advantageous variants, such as this chimeric P450 enzyme with an altered substrate specificity leading to a potent resistance mechanism.
Recurrent slow slip event likely hastened by the 2011 Tohoku earthquake
Authors: Hirose Hitoshi , Kimura Hisanori , Enescu Bogdan , Aoi Shin
Published: September 2012

Slow slip events (SSEs) are another mode of fault deformation than the fast faulting of regular earthquakes. Such transient episodes have been observed at plate boundaries in a number of subduction zones around the globe. The SSEs near the Boso Peninsula, central Japan, are among the most documented SSEs, with the longest repeating history, of almost 30 y, and have a recurrence interval of 5 to 7 y. A remarkable characteristic of the slow slip episodes is the accompanying earthquake swarm activity. Our stable, long-term seismic observations enable us to detect SSEs using the recorded earthquake catalog, by considering an earthquake swarm as a proxy for a slow slip episode. Six recurrent episodes are identified in this way since 1982. The average duration of the SSE interoccurrence interval is 68 mo; however, there are significant fluctuations from this mean. While a regular cycle can be explained using a simple physical model, the mechanisms that are responsible for the observed fluctuations are poorly known. Here we show that the latest SSE in the Boso Peninsula was likely hastened by the stress transfer from the March 11, 2011 great Tohoku earthquake. Moreover, a similar mechanism accounts for the delay of an SSE in 1990 by a nearby earthquake. The low stress buildups and drops during the SSE cycle can explain the strong sensitivity of these SSEs to stress transfer from external sources.
Antibody-free, targeted mass-spectrometric approach for quantification of proteins at low picogram per milliliter levels in human plasma/serum
Authors: Shi Tujin , Fillmore Thomas L. , Sun Xuefei , Zhao Rui , Schepmoes Athena A. , Hossain Mahmud , Xie Fang , Wu Si , Kim Jong-Seo , Jones Nathan , Moore Ronald J. , Paša-Tolić Ljiljana , Kagan Jacob , Rodland Karin D. , Liu Tao , Tang Keqi , Camp David G. , Smith Richard D. , Qian Wei-Jun
Published: September 2012

Sensitive detection of low-abundance proteins in complex biological samples has typically been achieved by immunoassays that use antibodies specific to target proteins; however, de novo development of antibodies is associated with high costs, long development lead times, and high failure rates. To address these challenges, we developed an antibody-free strategy that involves PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing) for sensitive selected reaction monitoring (SRM)–based targeted protein quantification. The strategy capitalizes on high-resolution reversed-phase liquid chromatographic separations for analyte enrichment, intelligent selection of target fractions via on-line SRM monitoring of internal standards, and fraction multiplexing before nano–liquid chromatography-SRM quantification. Application of this strategy to human plasma/serum demonstrated accurate and reproducible quantification of proteins at concentrations in the 50–100 pg/mL range, which represents a major advance in the sensitivity of targeted protein quantification without the need for specific-affinity reagents. Application to a set of clinical serum samples illustrated an excellent correlation between the results obtained from the PRISM-SRM assay and those from clinical immunoassay for the prostate-specific antigen level.
Molecular mechanism of pancreatic tumor metastasis inhibition by Gd@C
82
(OH)
22
and its implication for de novo design of nanomedicine
Authors: Kang Seung-gu , Zhou Guoqiang , Yang Ping , Liu Ying , Sun Baoyun , Huynh Tien , Meng Huan , Zhao Lina , Xing Gengmei , Chen Chunying , Zhao Yuliang , Zhou Ruhong
Published: September 2012

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral metallofullerenol Gd@C
82
(OH)
22
can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C
82
(OH)
22
effectively blocks tumor growth in human pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also show Gd@C
82
(OH)
22
not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics simulations to illustrate the molecular mechanism by studying the Gd@C
82
(OH)
22
–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C
82
(OH)
22
inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C
82
(OH)
22
exhibits specific binding modes near the ligand-specificity loop S1′, thereby inhibiting MMP-9 activity. Both the suppression of MMP expression and specific binding mode make Gd@C
82
(OH)
22
a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic sites directly but fail in selective inhibition. Our findings provide insights for de novo design of nanomedicines for fatal diseases such as pancreatic cancer.
Skeletal parasympathetic innervation communicates central IL-1 signals regulating bone mass accrual
Authors: Bajayo Alon , Bar Arik , Denes Adam , Bachar Marilyn , Kram Vardit , Attar-Namdar Malka , Zallone Alberta , Kovács Krisztina J. , Yirmiya Raz , Bab Itai
Published: September 2012

Bone mass accrual is a major determinant of skeletal mass, governed by bone remodeling, which consists of bone resorption by osteoclasts and bone formation by osteoblasts. Bone mass accrual is inhibited by sympathetic signaling centrally regulated through activation of receptors for serotonin, leptin, and ACh. However, skeletal activity of the parasympathetic nervous system (PSNS) has not been reported at the bone level. Here we report skeletal immune-positive fibers for the PSNS marker vesicular ACh transporter (VAChT). Pseudorabies virus inoculated into the distal femoral metaphysis is identifiable in the sacral intermediolateral cell column and central autonomic nucleus, demonstrating PSNS femoral innervation originating in the spinal cord. The PSNS neurotransmitter ACh targets nicotinic (nAChRs), but not muscarinic receptors in bone cells, affecting mainly osteoclasts. nAChR agonists up-regulate osteoclast apoptosis and restrain bone resorption. Mice deficient of the α
2
nAChR subunit have increased bone resorption and low bone mass. Silencing of the IL-1 receptor signaling in the central nervous system by brain-specific overexpression of the human IL-1 receptor antagonist (
hIL1ra

Ast

+/+

mice) leads to very low skeletal VAChT expression and ACh levels. These mice also exhibit increased bone resorption and low bone mass. In WT but not in
hIL1ra

Ast

+/+

mice, the cholinergic ACh esterase inhibitor pyridostigmine increases ACh levels and bone mass apparently by inhibiting bone resorption. Taken together, these results identify a previously unexplored key central IL-1–parasympathetic–bone axis that antagonizes the skeletal sympathetic tone, thus potently favoring bone mass accrual.
Tension induces a base-paired overstretched DNA conformation
Authors: Bosaeus Niklas , El-Sagheer Afaf H. , Brown Tom , Smith Steven B. , Åkerman Björn , Bustamante Carlos , Nordén Bengt
Published: September 2012

Mixed-sequence DNA molecules undergo mechanical overstretching by approximately 70% at 60–70 pN. Since its initial discovery 15 y ago, a debate has arisen as to whether the molecule adopts a new form [Cluzel P, et al. (1996)
Science
271:792–794; Smith SB, Cui Y, Bustamante C (1996)
Science
271:795–799], or simply denatures under tension [van Mameren J, et al. (2009) Proc Natl Acad Sci USA 106:18231–18236]. Here, we resolve this controversy by using optical tweezers to extend small 60–64 bp single DNA duplex molecules whose base content can be designed at will. We show that when AT content is high (70%), a force-induced denaturation of the DNA helix ensues at 62 pN that is accompanied by an extension of the molecule of approximately 70%. By contrast, GC-rich sequences (60% GC) are found to undergo a reversible overstretching transition into a distinct form that is characterized by a 51% extension and that remains base-paired. For the first time, results proving the existence of a stretched basepaired form of DNA can be presented. The extension observed in the reversible transition coincides with that produced on DNA by binding of bacterial RecA and human Rad51, pointing to its possible relevance in homologous recombination.
Monkeys benefit from reciprocity without the cognitive burden
Authors: Suchak Malini , de Waal Frans B. M.
Published: September 2012

The debate about the origins of human prosociality has focused on the presence or absence of similar tendencies in other species, and, recently, attention has turned to the underlying mechanisms. We investigated whether direct reciprocity could promote prosocial behavior in brown capuchin monkeys (Cebus apella). Twelve capuchins tested in pairs could choose between two tokens, with one being “prosocial” in that it rewarded both individuals (i.e., 1/1), and the other being “selfish” in that it rewarded the chooser only (i.e., 1/0). Each monkey’s choices with a familiar partner from their own group was compared with choices when paired with a partner from a different group. Capuchins were spontaneously prosocial, selecting the prosocial option at the same rate regardless of whether they were paired with an in-group or out-group partner. This indicates that interaction outside of the experimental setting played no role. When the paradigm was changed, such that both partners alternated making choices, prosocial preference significantly increased, leading to mutualistic payoffs. As no contingency could be detected between an individual’s choice and their partner’s previous choice, and choices occurred in rapid succession, reciprocity seemed of a relatively vague nature akin to mutualism. Having the partner receive a better reward than the chooser (i.e., 1/2) during the alternating condition increased the payoffs of mutual prosociality, and prosocial choice increased accordingly. The outcome of several controls made it hard to explain these results on the basis of reward distribution or learned preferences, and rather suggested that joint action promotes prosociality, resulting in so-called attitudinal reciprocity.
Lateralization of observational fear learning at the cortical but not thalamic level in mice
Authors: Kim Sangwoo , Mátyás Ferenc , Lee Sukchan , Acsády László , Shin Hee-Sup
Published: September 2012

Major cognitive and emotional faculties are dominantly lateralized in the human cerebral cortex. The mechanism of this lateralization has remained elusive owing to the inaccessibility of human brains to many experimental manipulations. In this study we demonstrate the hemispheric lateralization of observational fear learning in mice. Using unilateral inactivation as well as electrical stimulation of the anterior cingulate cortex (ACC), we show that observational fear learning is controlled by the right but not the left ACC. In contrast to the cortex, inactivation of either left or right thalamic nuclei, both of which are in reciprocal connection to ACC, induced similar impairment of this behavior. The data suggest that lateralization of negative emotions is an evolutionarily conserved trait and mainly involves cortical operations. Lateralization of the observational fear learning behavior in a rodent model will allow detailed analysis of cortical asymmetry in cognitive functions.
Post-translational modifications induce significant yet not extreme changes to protein structure
Authors: Xin Fuxiao , Radivojac Predrag
Published: September 2012

Motivation: A number of studies of individual proteins have shown that post-translational modifications (PTMs) are associated with structural rearrangements of their target proteins. Although such studies provide critical insights into the mechanics behind the dynamic regulation of protein function, they usually feature examples with relatively large conformational changes. However, with the steady growth of Protein Data Bank (PDB) and available PTM sites, it is now possible to more systematically characterize the role of PTMs as conformational switches. In this study, we ask (1) what is the expected extent of structural change upon PTM, (2) how often are those changes in fact substantial, (3) whether the structural impact is spatially localized or global and (4) whether different PTMs have different signatures.

Results: We exploit redundancy in PDB and, using root-mean-square deviation, study the conformational heterogeneity of groups of protein structures corresponding to identical sequences in their unmodified and modified forms. We primarily focus on the two most abundant PTMs in PDB, glycosylation and phosphorylation, but show that acetylation and methylation have similar tendencies. Our results provide evidence that PTMs induce conformational changes at both local and global level. However, the proportion of large changes is unexpectedly small; only 7% of glycosylated and 13% of phosphorylated proteins undergo global changes >2 Å. Further analysis suggests that phosphorylation stabilizes protein structure by reducing global conformational heterogeneity by 25%. Overall, these results suggest a subtle but common role of allostery in the mechanisms through which PTMs affect regulatory and signaling pathways.

Contact:  predrag@indiana.edu

Supplementary Information: Supplementary data are available at Bioinformatics online.
Hatred and Profits: Under the Hood of the Ku Klux Klan*
Authors: Fryer Roland G. , Levitt Steven D.
Published: August 2012

In this article, we analyze the 1920s Ku Klux Klan, those who joined it, and its social and political impact by combining a wide range of archival data sources with data from the 1920 and 1930 U.S censuses. We find that individuals who joined the Klan in some cities were more educated and more likely to hold professional jobs than the typical American. Surprisingly, we find little evidence that the Klan had an effect on black or foreign-born residential mobility or vote totals. Rather than a terrorist organization, the 1920s Klan is best described as social organization with a very successful multilevel marketing structure fueled by an army of highly incentivized sales agents selling hatred, religious intolerance, and fraternity in a time and place where there was tremendous demand.
Production and Release of Asexual Sporangia in Plasmopara viticola
Authors: Caffi Tito , Gilardi Giovanna , Monchiero Matteo , Rossi Vittorio
Published: September 2012

To study the influence of environmental conditions on sporulation of Plasmopara viticola lesions under vineyard's conditions, unsprayed vines were inspected every second or third day and the numbers of sporulating and nonsporulating lesions were counted in two North Italy vineyards in 2008 to 2010. Infected leaves were removed so that only fresh lesions were assessed at each field assessment. Sporulation was studied at two scales, across field assessments and across the seasonal population of lesions. Frequencies of sporulating lesions were positively correlated with the numbers of moist hours in the preceding dark period (i.e., the number of hours between 8:00 p.m. and 7:00 a.m. with relative humidity ≥80%, rainfall >0 mm, or wetness duration >30 min). In a receiver operating characteristic analysis, predicted sporulation based on the occurrence of ≥3 moist hours at night provided overall accuracy of 0.85. To study the time course of sporulation on lesions which were not washed by rainfall, numbers of sporangia produced per square millimeter of lesion were estimated on individual cohorts of lesions over the whole infectious period. The numbers of sporangia per square millimeter of lesion increased rapidly during the first 4 days after the beginning of sporulation and then tapered off prior to a halt; the time course of cumulative sporangia production by a lesion followed a monomolecular growth model (R2 = 0.97). The total number of sporangia produced by a square millimeter of lesion increased as the maximum temperature decreased and moist hours in the dark increased. To study the release pattern of the sporangia, spore samplers were placed near grapevines with sporulating lesions. Airborne sporangia were caught in 91.2% of the days over a wide range of weather conditions, including rainless periods. The results of this study provide quantitative information on production of P. viticola sporangia that may help refine epidemiological models used as decision aids in grape disease management programs.
Frigatebird behaviour at the ocean–atmosphere interface: integrating animal behaviour with multi-satellite data
Authors: De Monte Silvia , Cotté Cedric , d'Ovidio Francesco , Lévy Marina , Le Corre Matthieu , Weimerskirch Henri
Published: September 2012

Marine top predators such as seabirds are useful indicators of the integrated response of the marine ecosystem to environmental variability at different scales. Large-scale physical gradients constrain seabird habitat. Birds however respond behaviourally to physical heterogeneity at much smaller scales. Here, we use, for the first time, three-dimensional GPS tracking of a seabird, the great frigatebird (Fregata minor), in the Mozambique Channel. These data, which provide at the same time high-resolution vertical and horizontal positions, allow us to relate the behaviour of frigatebirds to the physical environment at the (sub-)mesoscale (10–100 km, days–weeks). Behavioural patterns are classified based on the birds’ vertical displacement (e.g. fast/slow ascents and descents), and are overlaid on maps of physical properties of the ocean–atmosphere interface, obtained by a nonlinear analysis of multi-satellite data. We find that frigatebirds modify their behaviours concurrently to transport and thermal fronts. Our results suggest that the birds’ co-occurrence with these structures is a consequence of their search not only for food (preferentially searched over thermal fronts) but also for upward vertical wind. This is also supported by their relationship with mesoscale patterns of wind divergence. Our multi-disciplinary method can be applied to forthcoming high-resolution animal tracking data, and aims to provide a mechanistic understanding of animals' habitat choice and of marine ecosystem responses to environmental change.
Ready steady slow: action preparation slows the subjective passage of time
Authors: Hagura Nobuhiro , Kanai Ryota , Orgs Guido , Haggard Patrick
Published: September 2012

Professional ball game players report the feeling of the ball ‘slowing-down’ before hitting it. Because effective motor preparation is critical in achieving such expert motor performance, these anecdotal comments imply that the subjective passage of time may be influenced by preparation for action. Previous reports of temporal illusions associated with action generally emphasize compensation for suppressed sensory signals that accompany motor commands. Here, we show that the time is perceived slowed-down during preparation of a ballistic reaching movement before action, involving enhancement of sensory processing. Preparing for a reaching movement increased perceived duration of a visual stimulus. This effect was tightly linked to action preparation, because the amount of temporal dilation increased with the information about the upcoming movement. Furthermore, we showed a reduction of perceived frequency for flickering stimuli and an enhanced detection of rapidly presented letters during action preparation, suggesting increased temporal resolution of visual perception during action preparation. We propose that the temporal dilation during action preparation reflects the function of the brain to maximize the capacity of sensory information-acquisition prior to execution of a ballistic movement. This strategy might facilitate changing or inhibiting the planned action in response to last-minute changes in the external environment.
A highly integrated and complex PPARGC1A transcription factor binding network in HepG2 cells
Authors: Charos Alexandra E. , Reed Brian D. , Raha Debasish , Szekely Anna M. , Weissman Sherman M. , Snyder Michael
Published: September 2012

PPARGC1A is a transcriptional coactivator that binds to and coactivates a variety of transcription factors (TFs) to regulate the expression of target genes. PPARGC1A plays a pivotal role in regulating energy metabolism and has been implicated in several human diseases, most notably type II diabetes. Previous studies have focused on the interplay between PPARGC1A and individual TFs, but little is known about how PPARGC1A combines with all of its partners across the genome to regulate transcriptional dynamics. In this study, we describe a core PPARGC1A transcriptional regulatory network operating in HepG2 cells treated with forskolin. We first mapped the genome-wide binding sites of PPARGC1A using chromatin-IP followed by high-throughput sequencing (ChIP-seq) and uncovered overrepresented DNA sequence motifs corresponding to known and novel PPARGC1A network partners. We then profiled six of these site-specific TF partners using ChIP-seq and examined their network connectivity and combinatorial binding patterns with PPARGC1A. Our analysis revealed extensive overlap of targets including a novel link between PPARGC1A and HSF1, a TF regulating the conserved heat shock response pathway that is misregulated in diabetes. Importantly, we found that different combinations of TFs bound to distinct functional sets of genes, thereby helping to reveal the combinatorial regulatory code for metabolic and other cellular processes. In addition, the different TFs often bound near the promoters and coding regions of each other's genes suggesting an intricate network of interdependent regulation. Overall, our study provides an important framework for understanding the systems-level control of metabolic gene expression in humans.
Deep sequencing of subcellular RNA fractions shows splicing to be predominantly co-transcriptional in the human genome but inefficient for lncRNAs
Authors: Tilgner Hagen , Knowles David G. , Johnson Rory , Davis Carrie A. , Chakrabortty Sudipto , Djebali Sarah , Curado João , Snyder Michael , Gingeras Thomas R. , Guigó Roderic
Published: September 2012

Splicing remains an incompletely understood process. Recent findings suggest that chromatin structure participates in its regulation. Here, we analyze the RNA from subcellular fractions obtained through RNA-seq in the cell line K562. We show that in the human genome, splicing occurs predominantly during transcription. We introduce the coSI measure, based on RNA-seq reads mapping to exon junctions and borders, to assess the degree of splicing completion around internal exons. We show that, as expected, splicing is almost fully completed in cytosolic polyA+ RNA. In chromatin-associated RNA (which includes the RNA that is being transcribed), for 5.6% of exons, the removal of the surrounding introns is fully completed, compared with 0.3% of exons for which no intron-removal has occurred. The remaining exons exist as a mixture of spliced and fewer unspliced molecules, with a median coSI of 0.75. Thus, most RNAs undergo splicing while being transcribed: “co-transcriptional splicing.” Consistent with co-transcriptional spliceosome assembly and splicing, we have found significant enrichment of spliceosomal snRNAs in chromatin-associated RNA compared with other cellular RNA fractions and other nonspliceosomal snRNAs. CoSI scores decrease along the gene, pointing to a “first transcribed, first spliced” rule, yet more downstream exons carry other characteristics, favoring rapid, co-transcriptional intron removal. Exons with low coSI values, that is, in the process of being spliced, are enriched with chromatin marks, consistent with a role for chromatin in splicing during transcription. For alternative exons and long noncoding RNAs, splicing tends to occur later, and the latter might remain unspliced in some cases.
ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia
Authors: Landt Stephen G. , Marinov Georgi K. , Kundaje Anshul , Kheradpour Pouya , Pauli Florencia , Batzoglou Serafim , Bernstein Bradley E. , Bickel Peter , Brown James B. , Cayting Philip , Chen Yiwen , DeSalvo Gilberto , Epstein Charles , Fisher-Aylor Katherine I. , Euskirchen Ghia , Gerstein Mark , Gertz Jason , Hartemink Alexander J. , Hoffman Michael M. , Iyer Vishwanath R. , Jung Youngsook L. , Karmakar Subhradip , Kellis Manolis , Kharchenko Peter V. , Li Qunhua , Liu Tao , Liu X. Shirley , Ma Lijia , Milosavljevic Aleksandar , Myers Richard M. , Park Peter J. , Pazin Michael J. , Perry Marc D. , Raha Debasish , Reddy Timothy E. , Rozowsky Joel , Shoresh Noam , Sidow Arend , Slattery Matthew , Stamatoyannopoulos John A. , Tolstorukov Michael Y. , White Kevin P. , Xi Simon , Farnham Peggy J. , Lieb Jason D. , Wold Barbara J. , Snyder Michael
Published: September 2012

Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals.
High-fidelity promoter profiling reveals widespread alternative promoter usage and transposon-driven developmental gene expression
Authors: Batut Philippe , Dobin Alexander , Plessy Charles , Carninci Piero , Gingeras Thomas R.
Published: August 2012

Many eukaryotic genes possess multiple alternative promoters with distinct expression specificities. Therefore, comprehensively annotating promoters and deciphering their individual regulatory dynamics is critical for gene expression profiling applications and for our understanding of regulatory complexity. We introduce RAMPAGE, a novel promoter activity profiling approach that combines extremely specific 5′-complete cDNA sequencing with an integrated data analysis workflow, to address the limitations of current techniques. RAMPAGE features a streamlined protocol for fast and easy generation of highly multiplexed sequencing libraries, offers very high transcription start site specificity, generates accurate and reproducible promoter expression measurements, and yields extensive transcript connectivity information through paired-end cDNA sequencing. We used RAMPAGE in a genome-wide study of promoter activity throughout 36 stages of the life cycle of Drosophila melanogaster, and describe here a comprehensive data set that represents the first available developmental time-course of promoter usage. We found that >40% of developmentally expressed genes have at least two promoters and that alternative promoters generally implement distinct regulatory programs. Transposable elements, long proposed to play a central role in the evolution of their host genomes through their ability to regulate gene expression, contribute at least 1300 promoters shaping the developmental transcriptome of D. melanogaster. Hundreds of these promoters drive the expression of annotated genes, and transposons often impart their own expression specificity upon the genes they regulate. These observations provide support for the theory that transposons may drive regulatory innovation through the distribution of stereotyped cis-regulatory modules throughout their host genomes.
A second-generation assembly of the Drosophila simulans genome provides new insights into patterns of lineage-specific divergence
Authors: Hu Tina T. , Eisen Michael B. , Thornton Kevin R. , Andolfatto Peter
Published: August 2012

We create a new assembly of the Drosophila simulans genome using 142 million paired short-read sequences and previously published data for strain w501. Our assembly represents a higher-quality genomic sequence with greater coverage, fewer misassemblies, and, by several indexes, fewer sequence errors. Evolutionary analysis of this genome reference sequence reveals interesting patterns of lineage-specific divergence that are different from those previously reported. Specifically, we find that Drosophila melanogaster evolves faster than D. simulans at all annotated classes of sites, including putatively neutrally evolving sites found in minimal introns. While this may be partly explained by a higher mutation rate in D. melanogaster, we also find significant heterogeneity in rates of evolution across classes of sites, consistent with historical differences in the effective population size for the two species. Also contrary to previous findings, we find that the X chromosome is evolving significantly faster than autosomes for nonsynonymous and most noncoding DNA sites and significantly slower for synonymous sites. The absence of a X/A difference for putatively neutral sites and the robustness of the pattern to Gene Ontology and sex-biased expression suggest that partly recessive beneficial mutations may comprise a substantial fraction of noncoding DNA divergence observed between species. Our results have more general implications for the interpretation of evolutionary analyses of genomes of different quality.
Drosophila insulin‐like peptide‐6 (dilp6) expression from fat body extends lifespan and represses secretion of Drosophila insulin‐like peptide‐2 from the brain
Authors: Bai Hua , Kang Ping , Tatar Marc
Published: August 2012

Reduced insulin/IGF signaling extends lifespan in diverse species, including Drosophila melanogaster where the genome encodes seven insulin‐like peptides (dilp1‐7). Of these, reduced dilp2 expressed in the brain has been associated with longevity assurance when over‐expression of dfoxo in fat bodies extends lifespan. Here, we show that the insulin‐regulated transcription factor dFOXO positively modulates dilp6 mRNA in adult fat body. Over‐expression of dilp6 in adult fat body extends lifespan and increases longevity‐associated metabolic phenotypes. Adult fat body dilp6 expression represses dilp2 and dilp5 mRNA in the brain, and the secretion of DILP2 into the hemolymph. The longevity benefit of expressing dfoxo in fat body, and the nonautonomous effect of fat body dfoxo upon brain dilp expression, is blocked by simultaneously repressing dilp6 by RNAi in fat body. dilp6 thus appears to bridge dFOXO, adipose tissue and brain endocrine function to regulate Drosophila longevity.
Decidual Stromal Cells as Regulators of T‐Cell Access to the Maternal–Fetal Interface
Authors: Silasi Michelle , Mor Gil
Published: August 2012

A recent study in the journal Science offers insights into the mechanism behind feto‐maternal tolerance, as evidenced by changes in the immuno‐logical environment of the uterus and decidua. They also provide a rich area of research for the understanding of the regulation of the immune system in other complicated medical conditions, including cancer and pregnancies affected by infection or autoimmunity.
Ocular allergy: recognizing and diagnosing hypersensitivity disorders of the ocular surface
Authors: Leonardi A. , Bogacka E. , Fauquert J. L. , Kowalski M. L. , Groblewska A. , Jedrzejczak‐Czechowicz M. , Doan S. , Marmouz F. , Demoly P. , Delgado L.
Published: September 2012

Ocular allergy includes several clinically different conditions that can be considered as hypersensitivity disorders of the ocular surface. The classification of these conditions is complex, and their epidemiology has not been adequately studied because of the lack of unequivocal nomenclature. Ocular allergy symptoms are often, but not always, associated with other allergic manifestations, mostly rhinitis. However, specific ocular allergic diseases need to be recognized and managed by a team that includes both an ophthalmologist and an allergist. The diagnosis of ocular allergy is usually based on clinical history and signs and symptoms, with the support of in vivo and in vitro tests when the identification of the specific allergic sensitization is required for patient management. The aims of this Task Force Report are (i) to unify the nomenclature and classification of ocular allergy, by combining the ophthalmology and allergy Allergic Rhinitis and its Impact on Asthma criteria; (ii) to describe current methods of diagnosis; (iii) to summarize the therapeutic options for the management of ocular allergic inflammation.
Myocardial calcium overload during graded hypothermia and after rewarming in an in vivo rat model
Authors: Wold R. M. , Kondratiev T. , Tveita T.
Published: September 2012

Aim

Mechanisms underlying cardiac contractile dysfunction during and after rewarming from hypothermia remain largely unknown. We have previously reported myocardial post‐hypothermic calcium overload to be the culprit. The aim of the present study was to measure changes in myocardial [Ca2+]i during graded hypothermia and after rewarming in an anesthetized, intact rat model, using the 45Ca2+ technique.

Methods

Rats were randomized and cooled to 15 °C. Hearts were excised and perfusion‐washed to remove extracellular calcium after 0.5 h of hypothermia (n = 9), 4 h of hypothermia (n = 8), and after 4 h of hypothermia and 2 h rewarming (n = 9). A normothermic group, kept at 37 °C for 5 h, served as control (n = 6). [Ca2+]i was determined in perchloric acid extracts of heart tissue. Spontaneous cardiac electromechanic work was maintained during hypothermia without cardiac arrest or ischaemia.

Results

Between 0.5 and 4 h at 15 °C, a six‐fold increase in cardiac [Ca2+]i was observed (0.55 ± 0.10 vs. 2.93 ± 0.76 μmol (g dry wt)−1). Rewarming resulted in a 33% decline in [Ca2+]i, but the actual value was significantly above the value measured in control hearts.

Conclusion

We show that calcium overload is a characteristic feature of the beating heart during deep hypothermia, which aggravates by increasing duration of exposure. The relatively low decline in [Ca2+]i during the rewarming period indicates difficulties in recovering calcium homoeostasis, which in turn may explain cardiac contractile dysfunction observed after rewarming.