bluuebunny/crossref_metadata_2025 huggingface dataset:
Examining organic carbon transport by the Orinoco River using SeaWiFS imagery
Authors: López Ramón , Del Castillo Carlos E. , Miller Richard L. , Salisbury Joseph , Wisser Dominik
Published: July 2012

The Orinoco River is the fourth largest in the world in terms of water discharge and organic carbon export to the ocean. River export of organic carbon is a key component of the carbon cycle and the global carbon budget. Here, we examined the seasonal transport of organic carbon by the Orinoco River into the eastern Caribbean using the conservative relationship of colored dissolved organic matter (CDOM) and dissolved organic carbon (DOC) in low salinity coastal waters influenced by river plumes. In situ measurements of CDOM absorption, DOC, and salinity were used to develop an empirical model for DOC concentration at the Orinoco River Plume. Satellite remote sensing reflectances were used with empirical models to determine DOC and Particulate organic carbon (POC) river transport. Our estimates of CDOM and DOC significantly correlated with in situ measurements and were within the expected ranges for the river. Total organic carbon transport by the Orinoco River during the period of 1998 to 2010 was 7.10 ×1012 g C y−1, from 5.29 × 1012 g C y−1 of DOC and 1.81 × 1012 g C y−1 of POC, representing ∼6% increase to previous published estimates. The variability in organic carbon transport responded to the seasonality in river flow more than to changes in organic carbon concentration in the river. Our results corroborate that is possible to estimate organic carbon transport using ocean color data at global scales. This is needed to reduce the uncertainties of land–ocean carbon fluxes.
An uplift history of the Colorado Plateau and its surroundings from inverse modeling of longitudinal river profiles
Authors: Roberts G. G. , White N. J. , Martin‐Brandis G. L. , Crosby A. G.
Published: July 2012

It is generally agreed that a region encompassing the Colorado Plateau has been uplifted by sub‐crustal processes. Admittance calculations, tomographic studies and receiver function analyses suggest that dynamic support is generated by some combination of convective upwelling and lithospheric thickness changes. Notwithstanding advances in our understanding of present‐day setting, uplift rate histories are poorly constrained and debated: an improved history will aid discrimination between proposed models. Here, we show that a regional uplift rate history can be obtained by inverting longitudinal river profiles. We assume that the shape of a river profile is controlled by uplift rate and moderated by erosion. In our model, uplift rate is allowed to vary smoothly as a function of space and time, upstream drainage area is invariant with time. Simultaneous inversion of river profiles from the Colorado, Rio Grande, Columbia and Mississippi catchments shows that three phases of regional uplift occurred. The first phase occurred between 80 and 50 Myrs, when ∼1 km of uplift was generated at a rate of ∼0.03 mm/yr. A second phase occurred between 35 and 15 Myrs, when ∼1.5 km of uplift was generated at a faster rate of ∼0.06 mm/yr. A final phase of uplift commenced ∼5 Myrs ago. These distinct phases of Late Cretaceous and Oligocene uplift are corroborated by stratigraphic considerations, by thermochronometric data, and by stratigraphic evidence of periodic clastic efflux delivered into the Gulf of Mexico. An episodic uplift history is consistent with staged removal of thick lithospheric mantle beneath a large region, which is currently centered on Yellowstone.
The young and happy marriage of membrane traffic and cell polarity
Authors: Thompson Barry J , Perez Franck , Vaccari Thomas
Published: July 2012

The ESF–EMBO meeting on ‘Cell Polarity and Membrane Traffic’ took place in Poland in April 2012. It brought together scientists from two once separate fields and highlighted their emerging interdependence. The wealth of scientific insights and discoveries presented laid a path for future research.
Measuring the societal impact of research
Authors: Bornmann Lutz
Published: July 2012

The global financial crisis has changed how nations and agencies prioritize research investment. There has been a push towards science with expected benefits for society, yet devising reliable tools to predict and measure the social impact of research remains a major challenge.
Phosphatidylinositol‐3 kinase activity in B cells is negatively regulated by Lyn tyrosine kinase
Authors: Xu Yuekang , Huntington Nicholas D , Harder Kenneth W , Nandurkar Harshal , Hibbs Margaret L , Tarlinton David M
Published: July 2012

Phosphatidylinositol‐3 kinase (PI3K) activity is essential for normal B‐cell receptor (BCR)‐mediated responses. To understand the mechanisms of PI3K regulation during B‐cell activation, we performed a series of biochemical analysis on primary B cells, and found that activity of Src family tyrosine kinases (SFK) is crucial for the activation of PI3K following BCR ligation and this is regulated by the SFK Lyn. We show that the hyperresponsive phenotype of B cells lacking Lyn is predicated on significantly increased basal and inducible PI3K activity that correlates with the constitutive hypophosphorylation of PAG/Cbp (phosphoprotein associated with glycosphingolipid‐enriched microdomains/Csk‐binding protein), a concomitant reduction in bound Csk in Lyn−/− B cells and elevated levels of active Fyn. Regulating SFK activity may thus be a central mechanism by which Lyn regulates PI3K activity in B cells. This study defines the molecular connection between the BCR and PI3K and reveals this to be a point of Lyn‐mediated regulation.
Identification of a haem domain in human soluble adenylate cyclase
Authors: Middelhaufe Sabine , Leipelt Martina , Levin Lonny R. , Buck Jochen , Steegborn Clemens
Published: July 2012

The second messengers cAMP and cGMP mediate a multitude of physiological processes. In mammals, these cyclic nucleotides are formed by related Class III nucleotidyl cyclases, and both ACs (adenylate cyclases) and GCs (guanylate cyclases) comprise transmembrane receptors as well as soluble isoforms. Whereas sGC (soluble GC) has a well-characterized regulatory HD (haem domain) that acts as a receptor for the activator NO (nitric oxide), very little is known about the regulatory domains of the ubiquitous signalling enzyme sAC (soluble AC). In the present study, we identify a unique type of HD as a regulatory domain in sAC. The sAC-HD (sAC haem domain) forms a larger oligomer and binds, non-covalently, one haem cofactor per monomer. Spectral analyses and mutagenesis reveal a 6-fold co-ordinated haem iron atom, probably with non-typical axial ligands, which can bind both NO and CO (carbon monoxide). Splice variants of sAC comprising this domain are expressed in testis and skeletal muscle, and the HD displays an activating effect on the sAC catalytic core. Our results reveal a novel mechanism for regulation of cAMP signalling and suggest a need for reanalysis of previous studies on mechanisms of haem ligand effects on cyclic nucleotide signalling, particularly in testis and skeletal muscle.
Microendoscopic Decompression Surgery for Lumbar Spinal Canal Stenosis via the Paramedian Approach: Preliminary Results
Authors: Nomura Kazunori , Yoshida Munehito
Published: July 2012

The objective of this study was to evaluate the efficacy of a microendoscopic spinal decompression surgical technique using a novel approach for the treatment of lumbar spinal canal stenosis (LSCS). The following modifications were made to the conventional microendoscopic bilateral decompression via the unilateral approach: the base of the spinous process was first resected partially to secure a working space, so as not to separate the spinous process from the lamina. The tip of the tubular retractor was placed at the midline of the lamina, where laminectomy was performed microendoscopically. A total of 126 stenotic levels were decompressed in 70 patients. The mean operating time per level was 77.0 minutes, and the mean intraoperative blood loss per level was 15.0 mL. There were no dural tears or neurological injuries intraoperatively. Fracture of the spinous process was detected postoperatively in two patients, both of whom were asymptomatic. All patients could be followed up for at least 12 months. Their median Japanese Orthopaedic Association (JOA) score improved significantly from 16 points preoperatively to 27.5 points after the surgery (p < 0.001). The case series showed that the modifications of the technique improved the safety and ease of performance of the microendoscopic decompression surgery for LSCS.
Comparison of Three-Dimensional Fluoroscopy versus Postoperative Computed Tomography for the Assessment of Accurate Screw Placement after Instrumented Spine Surgery
Authors: Garber Sarah T. , Bisson Erica F. , Schmidt Meic H.
Published: July 2012

While intraoperative three-dimensional fluoroscopy does not possess the resolution and image quality of computed tomography (CT), it may provide adequate information about screw placement to guide intra- and postoperative decision making. We compared the accuracy of intraoperative three-dimensional fluoroscopy visualization of proper screw placement with that of postoperative CT. We retrospectively reviewed spinal instrumentation procedures done using the O-arm (Medtronic, Minneapolis, MN, USA) that also had postoperative CT. All screws were assessed for placement accuracy on O-arm and CT images on a 4-point scale. In this study, 20 cases met the inclusion criteria. Thirteen breaches (11 grade 1 and 2 grade 2) were identified on O-arm images, and 14 breaches (10 grade 1, 3 grade 2, and 1 grade 3) were identified on CT. Sensitivity, specificity, and positive and negative predictive values were 93, 99, 99, and 98%, respectively. The Kappa value (0.96) suggested a very high degree of agreement between three-dimensional fluoroscopy and CT in determining accuracy of screw placement. These findings may allow less frequent use of postoperative CT scans, improving cost effectiveness in patients who require spinal instrumentation procedures and potentially decreasing the number of patients who require replacement of an inappropriately positioned screw.
On the Rules of Integration of Crowded Orientation Signals
Authors: Põder Endel
Published: July 2012

Crowding is related to an integration of feature signals over an inappropriately large area in the visual periphery. The rules of this integration are still not well understood. This study attempts to understand how the orientation signals from the target and flankers are combined. A target Gabor, together with 2, 4, or 6 flanking Gabors, was briefly presented in a peripheral location (4° eccentricity). The observer's task was to identify the orientation of the target (eight-alternative forced-choice). Performance was found to be nonmonotonically dependent on the target–flanker orientation difference (a drop at intermediate differences). For small target–flanker differences, a strong assimilation bias was observed. An effect of the number of flankers was found for heterogeneous flankers only. It appears that different rules of integration are used, dependent on some salient aspects (target pop-out, homogeneity–heterogeneity) of the stimulus pattern. The strategy of combining simple rules may be explained by the goal of the visual system to encode potentially important aspects of a stimulus with limited processing resources and using statistical regularities of the natural visual environment.
Understanding small-scale features in DGT measurements in sediments
Authors: Sochaczewski Łukasz , Davison William , Zhang Hao , Tych Wlodeck
Published: July 2012

Environmental context. Observations, using the technique of diffusive gradients in thin-films (DGT), of pronounced, small-scale (millimetre) maxima in concentrations of sulfide and metals in the pore water of sediments, have emphasised the importance of processes occurring in microniches. Modelling of the interactions between microniche sources and DGT devices within a sediment environment demonstrates how these sharp features arise and provides a basis for their quantitative interpretation.
Abstract. Measurements in sediments made using DGT (diffusive gradients in thin-films) have shown small-scale (millimetre and sub-millimetre) maxima in solute concentration (e.g trace metals and sulfide). The sediment–DGT system was simulated using a dynamic model, which incorporated a spherical microniche close to the DGT surface. DGT maxima could arise when the microniche was (1) a local source with associated elevated concentration in the pore water, and (2) when, within the microniche, the Kd for the relevant solute partitioning with exchangeable solute associated with the solid phase was much higher than for the rest of the sediment. Use of realistic values of Kd and comparison with existing data suggested that the latter mechanism was unlikely to be responsible for observed DGT maxima. Locally elevated concentrations will be reasonably accurately reproduced by DGT. Peak height measured by DGT will be between 62 and 87% of the true maxima in concentration within the sediment when DGT is not present, while peak widths will be similar. This work provides, for the first time, a means for confidently interpreting the two dimensional images of DGT-measured concentrations in sediments.
Inositol hexakisphosphate suppresses excitatory neurotransmission via synaptotagmin-1 C2B domain in the hippocampal neuron
Authors: Yang Shao-Nian , Shi Yue , Yang Guang , Li Yuxin , Yu Lina , Shin Ok-Ho , Bacaj Taulant , Südhof Thomas C. , Yu Jia , Berggren Per-Olof
Published: July 2012

Inositol hexakisphosphate (InsP
6
) levels rise and fall with neuronal excitation and silence, respectively, in the hippocampus, suggesting potential signaling functions of this inositol polyphosphate in hippocampal neurons. We now demonstrate that intracellular application of InsP
6
caused a concentration-dependent inhibition of autaptic excitatory postsynaptic currents (EPSCs) in cultured hippocampal neurons. The treatment did not alter the size and replenishment rate of the readily releasable pool in autaptic neurons. Intracellular exposure to InsP
6
did not affect spontaneous EPSCs or excitatory amino acid-activated currents in neurons lacking autapses. The InsP
6
-induced inhibition of autaptic EPSCs was effectively abolished by coapplication of an antibody to synaptotagmin-1 C2B domain. Importantly, preabsorption of the antibody with a GST-WT synaptotagmin-1 C2B domain fragment but not with a GST-mutant synaptotagmin-1 C2B domain fragment that poorly reacted with the antibody impaired the activity of the antibody on the InsP
6
-induced inhibition of autaptic EPSCs. Furthermore, K
+
depolarization significantly elevated endogenous levels of InsP
6
and occluded the inhibition of autaptic EPSCs by exogenous InsP
6
. These data reveal that InsP
6
suppresses excitatory neurotransmission via inhibition of the presynaptic synaptotagmin-1 C2B domain-mediated fusion via an interaction with the synaptotagmin Ca
2+
-binding sites rather than via interference with presynaptic Ca
2+
levels, synaptic vesicle trafficking, or inactivation of postsynaptic ionotropic glutamate receptors. Therefore, elevated InsP
6
in activated neurons serves as a unique negative feedback signal to control hippocampal excitatory neurotransmission.
Plasminogen activator inhibitor 1 - insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence
Authors: Elzi David J. , Lai Yanlai , Song Meihua , Hakala Kevin , Weintraub Susan T. , Shiio Yuzuru
Published: July 2012

Cellular senescence is widely believed to play a key role in tumor suppression, but the molecular pathways that regulate senescence are only incompletely understood. By using a secretome proteomics approach, we identified insulin-like growth factor binding protein 3 (IGFBP3) as a secreted mediator of breast cancer senescence upon chemotherapeutic drug treatment. The senescence-inducing activity of IGFBP3 is inhibited by tissue-type plasminogen activator-mediated proteolysis, which is counteracted by plasminogen activator inhibitor 1 (PAI-1), another secreted mediator of senescence. We demonstrate that IGFBP3 is a critical downstream target of PAI-1-induced senescence. These results suggest a role for an extracellular cascade of secreted proteins in the regulation of cellular senescence.
Geochemical evidence for possible natural migration of Marcellus Formation brine to shallow aquifers in Pennsylvania
Authors: Warner Nathaniel R. , Jackson Robert B. , Darrah Thomas H. , Osborn Stephen G. , Down Adrian , Zhao Kaiguang , White Alissa , Vengosh Avner
Published: July 2012

The debate surrounding the safety of shale gas development in the Appalachian Basin has generated increased awareness of drinking water quality in rural communities. Concerns include the potential for migration of stray gas, metal-rich formation brines, and hydraulic fracturing and/or flowback fluids to drinking water aquifers. A critical question common to these environmental risks is the hydraulic connectivity between the shale gas formations and the overlying shallow drinking water aquifers. We present geochemical evidence from northeastern Pennsylvania showing that pathways, unrelated to recent drilling activities, exist in some locations between deep underlying formations and shallow drinking water aquifers. Integration of chemical data (Br, Cl, Na, Ba, Sr, and Li) and isotopic ratios (
87
Sr/
86
Sr,
2
H/H,
18
O/
16
O, and
228
Ra/
226
Ra) from this and previous studies in 426 shallow groundwater samples and 83 northern Appalachian brine samples suggest that mixing relationships between shallow ground water and a deep formation brine causes groundwater salinization in some locations. The strong geochemical fingerprint in the salinized (Cl > 20 mg/L) groundwater sampled from the Alluvium, Catskill, and Lock Haven aquifers suggests possible migration of Marcellus brine through naturally occurring pathways. The occurrences of saline water do not correlate with the location of shale-gas wells and are consistent with reported data before rapid shale-gas development in the region; however, the presence of these fluids suggests conductive pathways and specific geostructural and/or hydrodynamic regimes in northeastern Pennsylvania that are at increased risk for contamination of shallow drinking water resources, particularly by fugitive gases, because of natural hydraulic connections to deeper formations.
Denaturant-dependent folding of GFP
Authors: Reddy Govardhan , Liu Zhenxing , Thirumalai D.
Published: July 2012

We use molecular simulations using a coarse-grained model to map the folding landscape of Green Fluorescent Protein (GFP), which is extensively used as a marker in cell biology and biotechnology. Thermal and Guanidinium chloride (GdmCl) induced unfolding of a variant of GFP, without the chromophore, occurs in an apparent two-state manner. The calculated midpoint of the equilibrium folding in GdmCl, taken into account using the Molecular Transfer Model (MTM), is in excellent agreement with the experiments. The melting temperatures decrease linearly as the concentrations of GdmCl and urea are increased. The structural features of rarely populated equilibrium intermediates, visible only in free energy profiles projected along a few order parameters, are remarkably similar to those identified in a number of ensemble experiments in GFP with the chromophore. The excellent agreement between simulations and experiments show that the equilibrium intermediates are stabilized by the chromophore. Folding kinetics, upon temperature quench, show that GFP first collapses and populates an ensemble of compact structures. Despite the seeming simplicity of the equilibrium folding, flux to the native state flows through multiple channels and can be described by the kinetic partitioning mechanism. Detailed analysis of the folding trajectories show that both equilibrium and several kinetic intermediates, including misfolded structures, are sampled during folding. Interestingly, the intermediates characterized in the simulations coincide with those identified in single molecule pulling experiments. Our predictions, amenable to experimental tests, show that MTM is a practical way to simulate the effect of denaturants on the folding of large proteins.
Simple few-state models reveal hidden complexity in protein folding
Authors: Beauchamp Kyle A. , McGibbon Robert , Lin Yu-Shan , Pande Vijay S.
Published: July 2012

Markov state models constructed from molecular dynamics simulations have recently shown success at modeling protein folding kinetics. Here we introduce two methods, flux PCCA+ (FPCCA+) and sliding constraint rate estimation (SCRE), that allow accurate rate models from protein folding simulations. We apply these techniques to fourteen massive simulation datasets generated by Anton and Folding@home. Our protocol quantitatively identifies the suitability of describing each system using two-state kinetics and predicts experimentally detectable deviations from two-state behavior. An analysis of the villin headpiece and FiP35 WW domain detects multiple native substates that are consistent with experimental data. Applying the same protocol to GTT, NTL9, and protein G suggests that some beta containing proteins can form long-lived native-like states with small register shifts. Even the simplest protein systems show folding and functional dynamics involving three or more states.
Adiponectin is critical in determining susceptibility to depressive behaviors and has antidepressant-like activity
Authors: Liu Jing , Guo Ming , Zhang Di , Cheng Shao-Ying , Liu Meilian , Ding Jun , Scherer Philipp E. , Liu Feng , Lu Xin-Yun
Published: July 2012

Depression is a debilitating mental illness and is often comorbid with metabolic disorders such as type 2 diabetes. Adiponectin is an adipocyte–derived hormone with antidiabetic and insulin-sensitizing properties. Here we show that adiponectin levels in plasma are reduced in a chronic social-defeat stress model of depression, which correlates with decreased social interaction time. A reduction in adiponectin levels caused by haploinsufficiency results in increased susceptibility to social aversion, “anhedonia,” and learned helplessness and causes impaired glucocorticoid-mediated negative feedback on the hypothalamic–pituitary–adrenal (HPA) axis. Intracerebroventricular (i.c.v.) injection of an adiponectin neutralizing antibody precipitates stress-induced depressive-like behavior. Conversely, i.c.v. administration of exogenous adiponectin produces antidepressant-like behavioral effects in normal-weight mice and in diet-induced obese diabetic mice. Taken together, these results suggest a critical role of adiponectin in depressive-like behaviors and point to a potential innovative therapeutic approach for depressive disorders.
Inactivation of a single gene enables microaerobic growth of the obligate anaerobe
Bacteroides fragilis
Authors: Meehan Brian M. , Baughn Anthony D. , Gallegos Rene , Malamy Michael H.
Published: July 2012

Bacteroides fragilis
can replicate in atmospheres containing ≤0.05% oxygen, but higher concentrations arrest growth by an unknown mechanism. Here we show that inactivation of a single gene,
oxe
(i.e., oxygen enabled) in
B. fragilis
allows for growth in concentrations as high as 2% oxygen while increasing the tolerance of this organism to room air. Known components of the oxidative stress response including the
ahpC
,
kat
,
batA-E
, and
tpx
genes were not individually important for microaerobic growth. However, a Δ
oxe
strain scavenged H
2
O
2
at a faster rate than WT, indicating that reactive oxygen species may play a critical role in limiting growth of this organism to low-oxygen environments. Clinical isolates of
B. fragilis
displayed a greater capacity for growth under microaerobic conditions than fecal isolates, with some encoding polymorphisms in
oxe
. Additionally, isolation of oxygen-enabled mutants of
Bacteroides thetaiotaomicron
suggests that Oxe may mediate growth arrest of other anaerobes in oxygenated environments.
A designed ankyrin repeat protein selected to bind to tubulin caps the microtubule plus end
Authors: Pecqueur Ludovic , Duellberg Christian , Dreier Birgit , Jiang Qiyang , Wang Chunguang , Plückthun Andreas , Surrey Thomas , Gigant Benoît , Knossow Marcel
Published: July 2012

Microtubules are cytoskeleton filaments consisting of αβ-tubulin heterodimers. They switch between phases of growth and shrinkage. The underlying mechanism of this property, called dynamic instability, is not fully understood. Here, we identified a designed ankyrin repeat protein (DARPin) that interferes with microtubule assembly in a unique manner. The X-ray structure of its complex with GTP-tubulin shows that it binds to the β-tubulin surface exposed at microtubule (+) ends. The details of the structure provide insight into the role of GTP in microtubule polymerization and the conformational state of tubulin at the very microtubule end. They show in particular that GTP facilitates the tubulin structural switch that accompanies microtubule assembly but does not trigger it in unpolymerized tubulin. Total internal reflection fluorescence microscopy revealed that the DARPin specifically blocks growth at the microtubule (+) end by a selective end-capping mechanism, ultimately favoring microtubule disassembly from that end. DARPins promise to become designable tools for the dissection of microtubule dynamic properties selective for either of their two different ends.
Enhancement of dendritic cell activation via CD40 ligand-expressing γδ T cells is responsible for protective immunity toPlasmodiumparasites
Authors: Inoue Shin-Ichi , Niikura Mamoru , Takeo Satoru , Mineo Shoichiro , Kawakami Yasushi , Uchida Akihiko , Kamiya Shigeru , Kobayashi Fumie
Published: July 2012

Previous reports have shown that γδ T cells are important for the elimination of malaria parasites in humans and mice. However, how γδ T cells are involved in protective immunity against blood-stage malaria remains unknown. We infected γδ T-cell–deficient (TCRδ-KO) mice and control wild-type mice withPlasmodium bergheiXAT, which is a nonlethal strain. Although infected red blood cells were eliminated within 30 d after infection, TCRδ-KO mice could not clear the infected red blood cells, showed high parasitemia, and eventually died. Therefore, γδ T cells are essential for clearance of the parasites. Here, we found that γδ T cells play a key role in dendritic cell activation afterPlasmodiuminfection. On day 5 postinfection, γδ T cells produced IFN-γ and expressed CD40 ligand during dendritic cell activation. These results suggest that γδ T cells enhance dendritic cell activation via IFN-γ and CD40 ligand–CD40 signaling. This hypothesis is supported strongly by the fact that in vivo induction of CD40 signaling prevented the death of TCRδ-KO mice after infection withP.bergheiXAT. This study improves our understanding of protective immunity against malaria and provides insights into γδ T-cell–mediated protective immunity against various infectious diseases.
Large enantiomeric excesses in primitive meteorites and the diverse effects of water in cosmochemical evolution
Authors: Pizzarello Sandra , Schrader Devin L. , Monroe Adam A. , Lauretta Dante S.
Published: July 2012

Carbonaceous chondrites are meteoritic fragments of asteroids that avoided the geological reprocessing of larger planets and allow laboratory probing of early solar-nebula materials. Among these, Renazzo-type (CR) chondrites found in Antarctica appear remarkably pristine and are distinguished by abundant organic materials and water-soluble molecules such as amino acids and ammonia. We present a comprehensive analysis of the organic composition of selected CR meteorites of different petrographic classification and compare compounds’ abundance and distribution as they may relate to asteroidal aqueous processing and concomitant evolution of the mineral phases. We found that several CR compounds such as amino acids and sugar alcohols are fully represented in stones with no or minimal water exposure indicating a formation that, if solar, preceded parent body processes. The most pristine CRs also revealed natal enantiomeric excesses (
ee
) of up to 60%, much larger than ever recorded. However, aqueous alteration appears to affect CR soluble organic composition and abundances, in particular some diastereomeric amino acids may gauge its extent by the consequent racemization of their
ee
.
Chemotactic signaling via carbohydrate phosphotransferase systems in
Escherichia coli
Authors: Neumann Silke , Grosse Karin , Sourjik Victor
Published: July 2012

Chemotaxis allows bacteria to follow gradients of nutrients, environmental stimuli, and signaling molecules, optimizing bacterial growth and survival.
Escherichia coli
has long served as a model of bacterial chemotaxis, and the signal processing by the core of its chemotaxis pathway is well understood. However, most of the research so far has focused on one branch of chemotactic signaling, in which ligands bind to periplasmic sensory domains of transmembrane chemoreceptors and induce a conformational change that is transduced across the membrane to regulate activity of the receptor-associated kinase CheA. Here we quantitatively characterize another, receptor-independent branch of chemotactic signaling that is linked to the sugar uptake through a large family of phosphotransferase systems (PTSs). Using in vivo characterization of intracellular signaling and protein interactions, we demonstrate that signals from cytoplasmic PTS components are transmitted directly to the sensory complexes formed by chemoreceptors, CheA and an adapter protein CheW. We further conclude that despite different modes of sensing, the PTS- and receptor-mediated signals have similar regulatory effects on the conformation of the sensory complexes. As a consequence, both types of signals become integrated and undergo common downstream processing including methylation-dependent adaptation. We propose that such mode of signaling is essential for efficient chemotaxis to PTS substrates and may be common to most bacteria.
Regulatory switch enforced by basic helix-loop-helix and ACT-domain mediated dimerizations of the maize transcription factor R
Authors: Kong Que , Pattanaik Sitakanta , Feller Antje , Werkman Joshua R. , Chai Chenglin , Wang Yongqin , Grotewold Erich , Yuan Ling
Published: July 2012

The maize R2R3-MYB regulator C1 cooperates with the basic helix–loop–helix (bHLH) factor R to activate the expression of anthocyanin biosynthetic genes coordinately. As is the case for other bHLH factors, R harbors several protein–protein interaction domains. Here we show that not the classical but rather a briefly extended R bHLH region forms homodimers that bind canonical G-box DNA motifs. This bHLH DNA-binding activity is abolished if the C-terminal ACT (aspartokinase, chorismate, and TyrA) domain is licensed to homodimerize. Then the bHLH remains in the monomeric form, allowing it to interact with R-interacting factor 1 (RIF1). In this configuration, the R–RIF1 complex is recruited to the promoters of a subset of anthocyanin biosynthetic genes, such as
A1
, through the interaction with its MYB partner C1. If, however, the ACT domain remains monomeric, the bHLH region dimerizes and binds to G-boxes present in several anthocyanin genes, such as
Bz1
. Our results provide a mechanism by which a dimerization domain in a bHLH factor behaves as a switch that permits distinct configurations of a regulatory complex to be tethered to different promoters. Such a combinatorial gene regulatory framework provides one mechanism by which genes lacking obviously conserved
cis
-regulatory elements are regulated coordinately.
Magnetic characterization of isolated candidate vertebrate magnetoreceptor cells
Authors: Eder Stephan H.K. , Cadiou Hervé , Muhamad Airina , McNaughton Peter A. , Kirschvink Joseph L. , Winklhofer Michael
Published: July 2012

Over the past 50 y, behavioral experiments have produced a large body of evidence for the existence of a magnetic sense in a wide range of animals. However, the underlying sensory physiology remains poorly understood due to the elusiveness of the magnetosensory structures. Here we present an effective method for isolating and characterizing potential magnetite-based magnetoreceptor cells. In essence, a rotating magnetic field is employed to visually identify, within a dissociated tissue preparation, cells that contain magnetic material by their rotational behavior. As a tissue of choice, we selected trout olfactory epithelium that has been previously suggested to host candidate magnetoreceptor cells. We were able to reproducibly detect magnetic cells and to determine their magnetic dipole moment. The obtained values (4 to 100 fAm
2
) greatly exceed previous estimates (0.5 fAm
2
). The magnetism of the cells is due to a μ
m
-sized intracellular structure of iron-rich crystals, most likely single-domain magnetite. In confocal reflectance imaging, these produce bright reflective spots close to the cell membrane. The magnetic inclusions are found to be firmly coupled to the cell membrane, enabling a direct transduction of mechanical stress produced by magnetic torque acting on the cellular dipole in situ. Our results show that the magnetically identified cells clearly meet the physical requirements for a magnetoreceptor capable of rapidly detecting small changes in the external magnetic field. This would also explain interference of ac powerline magnetic fields with magnetoreception, as reported in cattle.
Hematopoietic-specific targeting of influenza A virus reveals replication requirements for induction of antiviral immune responses
Authors: Langlois Ryan A. , Varble Andrew , Chua Mark A. , García-Sastre Adolfo , tenOever Benjamin R.
Published: July 2012

A coordinated innate and adaptive immune response, orchestrated by antigen presenting cells (APCs), is required for effective clearance of influenza A virus (IAV). Although IAV primarily infects epithelial cells of the upper respiratory tract, APCs are also susceptible. To determine if virus transcription in these cells is required to generate protective innate and adaptive immune responses, we engineered IAV to be selectively attenuated in cells of hematopoietic origin. Incorporation of hematopoietic-specific miR-142 target sites into the nucleoprotein of IAV effectively silenced virus transcription in APCs, but had no significant impact in lung epithelial cells. Here we demonstrate that inhibiting IAV replication in APCs in vivo did not alter clearance, or the generation of IAV-specific CD8 T cells, suggesting that cross-presentation is sufficient for cytotoxic T lymphocyte activation. In contrast, loss of in vivo virus infection, selectively in APCs, resulted in a significant reduction of retinoic acid-inducible gene I-dependent type I IFN (IFN-I). These data implicate the formation of virus replication intermediates in APCs as the predominant trigger of IFN-I in vivo. Taking these data together, this research describes a unique platform to study the host response to IAV and provides insights into the mechanism of antigen presentation and the induction of IFN-I.
RETRACTED: Stabilization of vaccines and antibiotics in silk and eliminating the cold chain
Authors: Zhang Jeney , Pritchard Eleanor , Hu Xiao , Valentin Thomas , Panilaitis Bruce , Omenetto Fiorenzo G. , Kaplan David L.
Published: July 2012

Sensitive biological compounds, such as vaccines and antibiotics, traditionally require a time-dependent “cold chain” to maximize therapeutic activity. This flawed process results in billions of dollars worth of viable drug loss during shipping and storage, and severely limits distribution to developing nations with limited infrastructure. To address these major limitations, we demonstrate self-standing silk protein biomaterial matrices capable of stabilizing labile vaccines and antibiotics, even at temperatures up to 60 °C over more than 6 months. Initial insight into the mechanistic basis for these findings is provided. Importantly, these findings suggest a transformative approach to the cold chain to revolutionize the way many labile therapeutic drugs are stored and utilized throughout the world.
APlasmodium-encoded cytokine suppresses T-cell immunity during malaria
Authors: Sun Tiffany , Holowka Thomas , Song Yan , Zierow Swen , Leng Lin , Chen Yibang , Xiong Huabao , Griffith Jason , Nouraie Mehdi , Thuma Philip E. , Lolis Elias , Janse Chris J. , Gordeuk Victor R. , Augustijn Kevin , Bucala Richard
Published: July 2012

The inability to acquire protective immunity againstPlasmodiais the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain ofPlasmodium berghei,we observed that thePlasmodiumortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2–associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate thatPlasmodiaactively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.
Experimental evidence showing that no mitotically active female germline progenitors exist in postnatal mouse ovaries
Authors: Zhang Hua , Zheng Wenjing , Shen Yan , Adhikari Deepak , Ueno Hiroo , Liu Kui
Published: July 2012

It has been generally accepted for more than half a century that, in most mammalian species, oocytes cannot renew themselves in postnatal or adult life, and that the number of oocytes is already fixed in fetal or neonatal ovaries. This assumption, however, has been challenged over the past decade. In this study, we have taken an endogenous genetic approach to this question and generated a multiple fluorescent

Rosa26
rbw/+
;Ddx4-Cre

germline reporter mouse model for in vivo and in vitro tracing of the development of female germline cell lineage. Through live cell imaging and de novo folliculogenesis experiments, we show that the Ddx4-expressing cells from postnatal mouse ovaries did not enter mitosis, nor did they contribute to oocytes during de novo folliculogenesis. Our results provide evidence that supports the traditional view that no postnatal follicular renewal occurs in mammals, and no mitotically active Ddx4-expressing female germline progenitors exist in postnatal mouse ovaries.
Transcriptome and methylome interactions in rice hybrids
Authors: Chodavarapu Ramakrishna K. , Feng Suhua , Ding Bo , Simon Stacey A. , Lopez David , Jia Yulin , Wang Guo-Liang , Meyers Blake C. , Jacobsen Steven E. , Pellegrini Matteo
Published: July 2012

DNA methylation is a heritable epigenetic mark that controls gene expression, is responsive to environmental stresses, and, in plants, may also play a role in heterosis. To determine the degree to which DNA methylation is inherited in rice, and how it both influences and is affected by transcription, we performed genome-wide measurements of these patterns through an integrative analysis of bisulfite-sequencing, RNA-sequencing, and siRNA-sequencing data in two inbred parents of the Nipponbare (NPB) and
indica
(93–11) varieties of rice and their hybrid offspring. We show that SNPs occur at a rate of about 1/253 bp between the two parents and that these are faithfully transmitted into the hybrids. We use the presence of these SNPs to reconstruct the two chromosomes in the hybrids according to their parental origin. We found that, unlike genetic inheritance, epigenetic heritability is quite variable. Cytosines were found to be differentially methylated (epimutated) at a rate of 7.48% (1/15 cytosines) between the NPB and 93–11 parental strains. We also observed that 0.79% of cytosines were epimutated between the parent and corresponding hybrid chromosome. We found that these epimutations are often clustered on the chromosomes, with clusters representing 20% of all epimutations between parental ecotypes, and 2–5% in F1 plants. Epimutation clusters are also strongly associated with regions where the production of siRNA differs between parents. Finally, we identified genes with both allele-specific expression patterns that were strongly inherited as well as those differentially expressed between hybrids and the corresponding parental chromosome. We conclude that much of the misinheritance of expression levels is likely caused by epimutations and
trans
effects.
Monkeys have a limited form of short-term memory in audition
Authors: Scott Brian H. , Mishkin Mortimer , Yin Pingbo
Published: July 2012

A stimulus trace may be temporarily retained either actively [i.e., in working memory (WM)] or by the weaker mnemonic process we will call passive short-term memory, in which a given stimulus trace is highly susceptible to “overwriting” by a subsequent stimulus. It has been suggested that WM is the more robust process because it exploits long-term memory (i.e., a current stimulus activates a stored representation of that stimulus, which can then be actively maintained). Recent studies have suggested that monkeys may be unable to store acoustic signals in long-term memory, raising the possibility that they may therefore also lack auditory WM. To explore this possibility, we tested rhesus monkeys on a serial delayed match-to-sample (DMS) task using a small set of sounds presented with ∼1-s interstimulus delays. Performance was accurate whenever a match or a nonmatch stimulus followed the sample directly, but it fell precipitously if a single nonmatch stimulus intervened between sample and match. The steep drop in accuracy was found to be due not to passive decay of the sample’s trace, but to retroactive interference from the intervening nonmatch stimulus. This “overwriting” effect was far greater than that observed previously in serial DMS with visual stimuli. The results, which accord with the notion that WM relies on long-term memory, indicate that monkeys perform serial DMS in audition remarkably poorly and that whatever success they had on this task depended largely, if not entirely, on the retention of stimulus traces in the passive form of short-term memory.
Insights into salt tolerance from the genome of
Thellungiella salsuginea
Authors: Wu Hua-Jun , Zhang Zhonghui , Wang Jun-Yi , Oh Dong-Ha , Dassanayake Maheshi , Liu Binghang , Huang Quanfei , Sun Hai-Xi , Xia Ran , Wu Yaorong , Wang Yi-Nan , Yang Zhao , Liu Yang , Zhang Wanke , Zhang Huawei , Chu Jinfang , Yan Cunyu , Fang Shuang , Zhang Jinsong , Wang Yiqin , Zhang Fengxia , Wang Guodong , Lee Sang Yeol , Cheeseman John M. , Yang Bicheng , Li Bo , Min Jiumeng , Yang Linfeng , Wang Jun , Chu Chengcai , Chen Shou-Yi , Bohnert Hans J. , Zhu Jian-Kang , Wang Xiu-Jie , Xie Qi
Published: July 2012

Thellungiella salsuginea,
a close relative of
Arabidopsis
, represents an extremophile model for abiotic stress tolerance studies. We present the draft sequence of the
T. salsuginea
genome, assembled based on ∼134-fold coverage to seven chromosomes with a coding capacity of at least 28,457 genes. This genome provides resources and evidence about the nature of defense mechanisms constituting the genetic basis underlying plant abiotic stress tolerance. Comparative genomics and experimental analyses identified genes related to cation transport, abscisic acid signaling, and wax production prominent in
T. salsuginea
as possible contributors to its success in stressful environments.
Discourse cohesion in text and tutorial dialogue
Authors: Graesser Arthur C. , Jeon Moongee , Yan Yan , Cai Zhiqiang
Published: July 2012

Discourse cohesion is presumably an important facilitator of comprehension when individuals read texts and hold conversations. This study investigated components of cohesion and language in different types of discourse about Newtonian physics: A textbook, textoids written by experimental psychologists, naturalistic tutorial dialoguebetween expert human tutors and college students, andAutoTutor tutorial dialogue between a computer tutor and students (AutoTutor is an animated pedagogical agent that helps students learn about physics by holding conversations in natural language). We analyzed the four types of discourse with Coh-Metrix, a software tool that measures discourse on different components of cohesion, language, and readability. The cohesion indices included co-reference, syntactic and semantic similarity, causal cohesion, incidence of cohesion signals (e.g., connectives, logical operators), and many other measures. Cohesion data were quite similar for the two forms of discourse in expository monologue (textbooks and textoids) and for the two types of tutorial dialogue (i.e., students interacting with human tutors and AutoTutor), but very different between the discourse of expository monologue and tutorial dialogue. Coh-Metrix was also able to detect subtle differences in the language and discourse of AutoTutor versus human tutoring.
Linguistics markers of coherence improve text comprehension in functional contexts
Authors: Sanders Ted , Land Jentine , Mulder Gerben
Published: July 2012

Text coherence can be marked linguistically by using connectives and lexical signals that make coherence relations explicit. This study focuses on the influence of such markers on text comprehension in ecologically valid contexts. A first experiment shows how readers in a business meeting and in a laboratory study benefit from the explicit marking of coherence relations. A second experiment shows how poor readers in secondary education benefit from coherence marking while answering text comprehension questions. We argue in favor of an interaction between cognitively oriented research on discourse representation and document design research, to solve crucial questions like: how do we design optimally readable texts?