bluuebunny/crossref_metadata_2025 huggingface dataset:
Millennial‐scale glacial meltwater pulses and their effect on the spatiotemporal benthicδ18O variability
Authors: Friedrich T. , Timmermann A.
Published: July 2012

Ratios of oxygen isotope values obtained from foraminiferal calcite are one of the most established paleoceanographic proxies. They are used in the context of estimating variations in ice volume, ocean temperature, and salinity and provide a means to date marine sediment cores across different ocean basins. Our study addresses the question how the δ18O of the deglacial meltwater signal propagates into the interior ocean, when large‐scale millennial‐scale reorganizations of the Atlantic Meridional Overturning Circulation (AMOC) are present. Analyzing a series of idealized tracer‐injection experiments conducted with an earth system model, we find that a substantial weakening of the AMOC leads to a massive delay in the export of the glacioeustatic oxygen isotope signal into the deep ocean, whereas the Atlantic‐Pacific lag in benthic oxygen isotope signals is not increased. Furthermore, it is shown that an AMOC cessation causes a decoupling ofδ18O propagation time and water mass age, in particular in the deep Pacific. Our results lend further support to the notion that benthic oxygen isotope records obtained from stacks are not a useful global chronostratigraphic tool during periods of millennial‐scale global ocean circulation changes. The regionally varying delay effect of the deglacial sea level signal studied here adds onto existing uncertainties in the interpretation and decomposition of benthic oxygen isotope in terms of sea level, temperature, and hydrographic variations.
Geomagnetically induced currents in the New Zealand power network
Authors: Marshall R. A. , Dalzell M. , Waters C. L. , Goldthorpe P. , Smith E. A.
Published: July 2012

Adverse space weather conditions have been shown to be directly responsible for faults within power networks at high latitudes. A number of studies have also shown space weather to impact power networks at lower latitudes, although most of these studies show increases in GIC activity within networks not directly related to hardware faults. This study examines a GIC event that occurred in New Zealand's South Island power network on 6th November 2001. A transformer failure that occurred during this day is shown to be associated with a change in the solar wind dynamic pressure of nearly 20 nPa. Measurements of GICs recorded on the neutral lines of transformers across the Transpower network during this event show good correlation with a GIC‐index, a proxy for the geoelectric field that drives GIC. Comparison of this event with GIC activity observed in the Transpower network during large space weather storms such as the “2003 Halloween storm,” suggests that solar wind shocks and associated geomagnetic sudden impulse (SI) events may be as hazardous to middle latitude power networks as GIC activity occurring during the main phase of large storms. Further, this study suggests that the latitudinal dependence of the impacts of SI events on power systems differs from that observed during large main phase storms. This study also highlights the importance of operating procedures for large space weather events, even at middle latitude locations.
Measurement depth of the cosmic ray soil moisture probe affected by hydrogen from various sources
Authors: Franz Trenton E. , Zreda M. , Ferre T. P. A. , Rosolem R. , Zweck C. , Stillman S. , Zeng X. , Shuttleworth W. J.
Published: July 2012

We present here a simple and robust framework for quantifying the effective sensor depth of cosmic ray soil moisture neutron probes such that reliable water fluxes may be computed from a time series of cosmic ray soil moisture. In particular, we describe how the neutron signal depends on three near‐surface hydrogen sources: surface water, soil moisture, and lattice water (water in minerals present in soil solids) and also their vertical variations. Through a combined modeling study of one‐dimensional water flow in soil and neutron transport in the atmosphere and subsurface, we compare average water content between the simulated soil moisture profiles and the universal calibration equation which is used to estimate water content from neutron counts. By using a linear sensitivity weighting function, we find that during evaporation and drainage periods the RMSE of the two average water contents is 0.0070 m3 m−3 with a maximum deviation of 0.010 m3 m−3 for a range of soil types. During infiltration, the RMSE is 0.011 m3 m−3 with a maximum deviation of 0.020 m3 m−3, where piston like flow conditions exists for the homogeneous isotropic media. Because piston flow is unlikely during natural conditions at the horizontal scale of hundreds of meters that is measured by the cosmic ray probe, this modeled deviation of 0.020 m3 m−3 represents the worst case scenario for cosmic ray sensing of soil moisture. Comparison of cosmic ray soil moisture data and a distributed sensor soil moisture network in Southern Arizona indicates an RMSE of 0.011 m3 m−3 over a 6 month study period.
Complement‐induced protection: an explanation for the limitations of cell‐based tumour immunotherapies
Authors: Kempshall Emma , Thebault Simon , Paul Morgan B , Harris Claire L , Gallimore Awen
Published: July 2012

Complement is involved in the inflammatory response and clearance of infected or altered cells. It is therefore unexpected that complement‐deficient animals are less susceptible to carcinogen‐induced tumours and more readily control growth of injected tumour cell lines than their wild‐type counterparts, implying that complement promotes tumour development and progression. Conversely, natural killer (NK) and CD8+ T cells are known to limit progression of the same tumours. Previous studies indicate that sublytic levels of the complement membrane attack complex protect cells against further attack by lytic doses of complement and other pore‐formers such as perforin. We hypothesise that inefficient attack by complement in vivo allows tumour cells to avoid lysis by both NK cells and antigen‐specific cytotoxic T cells, thereby promoting tumour outgrowth. Complement could thus be limiting the efficacy of NK and T cell‐targeted cancer therapies, and the inclusion of complement inhibitors could optimise these immunotherapeutic regimes.
Inhibition of GSK‐3β enhances neural differentiation in unrestricted somatic stem cells
Authors: Dastjerdi Fatemeh Vahid , Zeynali Bahman , Tafreshi Azita Parvaneh , Shahraz Anahita , Chavoshi Mahin Sadat , Najafabadi Irandokht Khaki , Vardanjani Marzieh Mowlavi , Atashi Amir , Soleimani Masoud
Published: July 2012

GSK‐3β is a key molecule in several signalling pathways, including the Wnt/β‐catenin signalling pathway. There is increasing evidence suggesting Wnt/β‐catenin signalling is involved in the neural differentiation of embryonic, somatic and neural stem cells. However, a large body of evidence indicates that this pathway maintains stem cells in a proliferative state. To address this controversy, we have investigated whether the Wnt/β‐catenin pathway is present and involved in the neural differentiation of newly introduced USSCs (unrestricted somatic stem cells). Our results indicate that the components of Wnt/β‐catenin signalling are present in undifferentiated USSCs. We also show that the treatment of neurally induced USSCs with BIO (6‐bromoindirubin‐3′‐oxime), a specific GSK‐3β inhibitor and Wnt activator, for 5 and 10 days results in increased expression of a general neuronal marker (β‐tubulin III). Moreover, the expression of pGSK‐3β and stabilized β‐catenin increased by BIO in neurally induced USSCs, indicates that the Wnt pathway is activated and functional in these cells. Thus, inhibition of GSK‐3β in USSCs enhances their neural differentiation, which suggests a positive role of the Wnt/β‐catenin signalling pathway towards neural fate.
Nuclear morphology and c‐Jun N‐terminal kinase 1 expression differentiate serum‐starved oxidative stress signalling from hydrogen peroxide‐induced apoptosis in retinal neuronal cell line
Authors: Basu Kaustuv , Mukhopadhyay Arijit , Ghosh Ilora , Datta Kasturi
Published: July 2012

Oxidative stress induced by serum starvation and H2O2 exposure, both triggers apoptosis in retinal neuronal cell line RGC‐5 (retinal ganglion cell‐5). We have examined whether, despite excess generation of ROS (reactive oxygen species) and apoptosis induction, there is any dissimilarity in nuclear morphology and apoptotic signalling pathway in RGC‐5 under these conditions. Sub‐confluent cells were treated either with H2O2 or maintained in SFM (serum‐free medium). ROS level was detected along with nuclear morphology and ultrastructural analysis. Generation of excess intracellular ROS, nuclear localization of Bax and caspase 3 activation along with decrease of cellular viability, confirmed apoptosis induction in RGC‐5 by 72 h serum starvation and 500 M H2O2 exposure for 1 h. Nuclear swelling as supported by nuclear cytoplasmic ratio and conspicuous black spots with nuclear remodelling were observed only upon SFM, but not with H2O2 treatment. Serum starvation did not alter JNK1 (c‐Jun N‐terminal kinase 1) expression, although nuclear translocation and higher level of pJNK (phospho‐JNK) was evident. Conversely, H2O2 exposure blocked the expression and activation of JNK1 to phospho‐JNK as a negligible level of pJNK was present in the cytoplasm. Despite similar ROS generation in both the conditions, difference in nuclear morphology and JNK1 expression leads to the hypothesis that RGC‐5 cells may follow different signalling pathways when challenged with serum starvation and H2O2.
Stabilisation of Cardiopulmonary Function in Newborns with Congenital Diaphragmatic Hernia Using Lung Function Parameters and Hemodynamic Management
Authors: Hofmann S. , Stadler K. , Heilmann A. , Häusler H. , Fitze G. , Kamin G. , Nitzsche K. , Hahn G. , Dinger J.
Published: July 2012

Evaluation of lung function parameters and additional use of prostaglandin E1 (PGE1) for the stabilisation of cardiopulmonary function in patients with congenital diaphragmatic hernia (CDH) and pulmonary hypertension (PHT).

Observational study.

Between 2007 and 2009 8 patients with CDH have been treated in our pediatric intensive care unit (gestational age 34 + 0 – 40 + 4 weeks, birth weight 2 160–3 840 g). All patients required respiratory support. Gentle mechanical ventilation adapted to the degree of pulmonary hypoplasia based on serially measurements of lung function parameters to find appropriate ventilator settings has been performed.

Functional residual capacity (FRC) and compliance of the respiratory system in all patients were markedly reduced. A FRC between 9.3–10.6 ml/kg and compliance between 1.1–1.8 ml/kPa/kg indicated pronounced hypoplasia of the lungs. Doppler flow patterns through the arterial duct were classified into left-to-right, right-to-left and bidirectional shunting and correlated to the degree of PHT. The additional use of PGE1 to reopen the arterial duct and to stabilize right ventricular function led to an amelioration of severe PHT and preoperative stabilisation in 2 newborns with pronounced pulmonary hypoplasia. All patients underwent successful surgery, and did not show any complications after 2 years follow-up.

Measurements of lung function parameters and adaptation of mechanical ventilation to the degree of pulmonary hypoplasia and additional therapy with PGE1 may help to improve the outcome in CDH patients.
Symptomatic Lumbar Disc Protrusion Causing Progressive Myelopathy in a Low-Lying Cord
Authors: Srinivas Shreya , Shetty Rohit , Collins Iona
Published: July 2012

Low-lying cord is an uncommon entity, and cord compression due lumbar disc disease is rarely encountered. We discuss our experience with a case of lumbar cord compression secondary to a large disc protrusion, which caused myelopathy in a low-lying/tethered cord. A 77-year-old woman with known spina bifida occulta presented with 6-week history of severe low back pain and progressive paraparesis. Magnetic resonance imaging showed a low-lying tethered cord and a large disc prolapse at L2/3 causing cord compression with associated syringomyelia. Medical comorbidities precluded her from anterior decompression, and therefore a posterior decompression was performed. She recovered full motor power in her lower limbs and could eventually walk unaided. She had a deep wound infection, which was successfully treated with debridement, negative pressure therapy (vacuum-assisted closure pump), and antibiotics. Six months after surgery, her Oswestry Disability Index improved from 55% preoperatively to 20%. Posterior spinal cord decompression for this condition has been successful in our case, and we believe that the lumbar lordosis may have helped indirectly decompress the spinal cord by posterior decompression alone.
High-Grade Adult Isthmic L5–S1 Spondylolisthesis: A Report of Intraoperative Slip Progression Treated with Surgical Reduction and Posterior Instrumented Fusion
Authors: Mikhael Mark M. , Shapiro Gary S. , Wang Jeffrey C.
Published: July 2012

Adult isthmic spondylolisthesis most commonly occurs at the L5–S1 level of the lumbar spine. Slip progression is relatively rare in adults with this condition and slippage is typically associated with advanced degeneration of the disk below the pars defect. When symptomatic, radiculopathy is the typical complaint in adults with isthmic spondylolisthesis. When considering options for surgical treatment of adult isthmic spondylolisthesis, the surgeon must consider several different options, such as decompression, fusion, instrumentation, reduction, and type of bone graft to be used. All of these decisions must be individualized as deemed appropriate for each particular patient. This report presents a case of intraoperative slip progression of a L5–S1 adult isthmic spondylolisthesis to a high-grade slip, which was treated with complete surgical reduction and posterior instrumented fusion. This case demonstrates the potential instability of this condition in adults and has not been previously reported. The case details and images are reviewed and the intraoperative decisions, treatment options, and patient outcome are discussed.
The Utility of Allograft Mesenchymal Stem Cells for Spine Fusion: A Literature Review
Authors: Lubelski Daniel , Abdullah Kalil G. , Benzel Edward C. , Mroz Thomas E.
Published: July 2012

More than 50% of patients complain of postoperative donor site morbidity following iliac crest bone graft harvest, and recent discoveries have identified adverse outcomes following bone morphogenetic protein use in spine fusion. This has led the spine community to turn toward alternative methods to promote fusion following spine surgery. The present article reviews numerous studies that have shown the osteogenic potential of mesenchymal stem cells (MSCs). MSCs have been used with both in vitro and in vivo models and have involved animal studies ranging from rats to macaque monkeys to successfully induce bone regeneration in lesions of the tibia and spine. There is no fear of graft rejection, as there may be with other allograft materials, because neither undifferentiated nor differentiated MSCs elicit lymphocyte response when transplanted; they tend to alter the cytokine profile to an anti-inflammatory state. Early clinical trials are underway with various commercially available MSC formulations. Although there is much enthusiasm, it is integral that the spine surgery community carefully evaluate the use of MSCs in spine fusion through well-designed and executed studies to determine the efficacy and safety profiles in spine surgery patients.
Cervical Total Disc Arthroplasty
Authors: Basho Rahul , Hood Kenneth A.
Published: July 2012

Symptomatic adjacent segment degeneration of the cervical spine remains problematic for patients and surgeons alike. Despite advances in surgical techniques and instrumentation, the solution remains elusive. Spurred by the success of total joint arthroplasty in hips and knees, surgeons and industry have turned to motion preservation devices in the cervical spine. By preserving motion at the diseased level, the hope is that adjacent segment degeneration can be prevented. Multiple cervical disc arthroplasty devices have come onto the market and completed Food and Drug Administration Investigational Device Exemption trials. Though some of the early results demonstrate equivalency of arthroplasty to fusion, compelling evidence of benefits in terms of symptomatic adjacent segment degeneration are lacking. In addition, non-industry-sponsored studies indicate that these devices are equivalent to fusion in terms of adjacent segment degeneration. Longer-term studies will eventually provide the definitive answer.
Thoracic Hyperkyphosis: Assessment of the Distal Fusion Level
Authors: Lundine Kristopher , Turner Peter , Johnson Michael
Published: July 2012

Study Design

This is a retrospective study.

Objective

The objective of this study was to assess the sagittal stable vertebra (SSV) versus the first lordotic vertebra (FLV) as the inferior fusion level in patients undergoing spinal surgery for thoracic hyperkyphosis. The main outcome of interest was the development of distal junctional kyphosis (DJK).

Summary of Background Data

Prior research has pointed to selection of the FLV for the distal instrumentation level in fusion for thoracic hyperkyphosis. In 2009, Cho et al introduced the concept of the SSV after recognizing the development of DJK despite fusion to the FLV.

Methods

Patients were reviewed who had undergone spinal fusion for thoracic hyperkyphosis. Preoperative radiographs were reviewed to assess thoracic kyphosis, lumbar lordosis, SSV, and FLV. Postoperative radiographs were reviewed to assess curve correction and whether patients developed DJK or implant failure.

Results

We reviewed 22 patients with a mean age at surgery of 18 (range 14 to 22). Mean preoperative kyphosis was 85 ± 14 degrees, and mean postoperative kyphosis at final follow-up was 59 ± 12 degrees for a mean correction of 26 ± 12 degrees. Eleven patients developed DJK and four patients experienced hardware failure. In 12 patients, the SSV was inferior to the FLV. Rates of DJK when the instrumentation included the SSV or FLV were 13 and 38%, respectively.

Conclusions

Fusion to the SSV is superior at preventing DJK when compared with fusion to the FLV.
Inception of an Australian Spine Trauma Registry: the Minimum Dataset
Authors: Tee J. W. , Chan C. H. P. , Gruen R. L. , Fitzgerald M. C. B. , Liew S. M. , Cameron P. A. , Rosenfeld J. V.
Published: July 2012

Background

The establishment of a spine trauma registry collecting both spine column and spinal cord data should improve the evidential basis for clinical decisions. This is a report on the pilot of a spine trauma registry including development of a minimum dataset.

Methods

A minimum dataset consisting of 56 data items was created using the modified Delphi technique. A pilot study was performed on 104 consecutive spine trauma patients recruited by the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR). Data analysis and collection methodology were reviewed to determine its feasibility.

Results

Minimum dataset collection aided by a dataset dictionary was uncomplicated (average of 5 minutes per patient). Data analysis revealed three significant findings: (1) a peak in the 40 to 60 years age group; (2) premorbid functional independence in the majority of patients; and (3) significant proportion being on antiplatelet or anticoagulation medications. Of the 141 traumatic spine fractures, the thoracolumbar segment was the most frequent site of injury. Most were neurologically intact (89%). Our study group had satisfactory 6-month patient-reported outcomes.

Conclusion

The minimum dataset had high completion rates, was practical and feasible to collect. This pilot study is the basis for the development of a spine trauma registry at the Level 1 trauma center.
Segmental Stiffness Achieved by Three Types of Fixation for Unstable Lumbar Spondylolytic Motion Segments
Authors: Choma Theodore , Pfeiffer Ferris , Vallurupalli Santaram , Mannering Irene , Pak Youngju
Published: July 2012

Objective

The objective of this study was to compare the relative stability in lumbar spondylolysis (SP) of a rigid anterior plate (with a novel compression slot) versus traditional posterior pedicle screw (PS) fixation.

Summary of Background Data

Arthrodesis has been a mainstay of treatment for symptomatic isthmic spondylolisthesis in adults. Posterior PS fixation has become a commonly used adjunct. Some have advocated anterior lumbar interbody fixation (ALIF) plate as an alternative. The relative stability afforded by ALIF in SP has not been well characterized, nor has the contribution afforded by a compression screw slot in an ALIF plate.

Methods

Calf spine segments were characterized in the normal state, after sectioning the pars (SP model), then after reconstruction with an interbody spacer and either PS/rods, or an ALIF plate, or both.

Results

ALIF plate conferred stability on the spondylolytic segment only comparable to that of the normal functional spinal unit (FSU). Posterior fixation was more stable than anterior fixation in all testing modes. Addition of an ALIF plate conferred a significant additional stability in those that already had posterior fixation. The utilization of an anterior compression screw conferred additional stability in extension testing only.

Conclusions

ALIF plate reconstruction in the setting of SP may not confer enough segmental stability to predictably encourage fusion beyond that of the uninstrumented intact FSU. The utilization of an integral compression screw in an ALIF plate may not confer clinically significant additional construct stability in SP.
The Incidence of Bifid C7 Spinous Processes
Authors: Cho Woojin , Maeda Takeshi , Park Yung , Buchowski Jacob M. , Nabb Colin E. , Riew Dan
Published: July 2012

For posterior cervical surgery, if the operation only involves the lower cervical area, counting from C2 is impractical and the level may not be visible on X-rays. In such cases, we usually place a marker at the top of the incision and also rely on the size and monofid shape of the C7 spinous process. Relying on the C7 morphology, however, we initially instrumented the wrong levels in a case where the patient had a bifid C7 spinous process. We therefore sought to determine the frequency of bifid cervicothoracic spinous processes. Computed tomography axial images of C6, C7, and T1 from 516 patients were evaluated. The spinous processes were classified into three categories: “bifid,” “partially bifid,” and “monofid.” C6 spinous process was monofid in 47.9% of cases, partially bifid in 4.2% of cases, and bifid in 47.9% of cases. C7 spinous process was monofid in 99.2% of cases, partially bifid in 0.5% of cases, and bifid in 0.3% of cases. T1 was monofid in all cases. A truly bifid C7 spinous process occurs 0.3% of the time and therefore is not a reliable landmark for choosing fusion levels. This knowledge hopefully helps prevent the type of wrong-level instrumentation that we performed.
Key Information Technology and Management Issues 2011–2012: An International Study
Authors: Luftman Jerry , Zadeh Hossein S , Derksen Barry , Santana Martin , Rigoni Eduardo Henrique , Huang Zhengwei (David)
Published: July 2012

The importance of the impact of IT for organizations around the world, especially in light of a very slow recovery from the global financial crisis, has amplified the need to provide a better understanding of the specific geographic similarities and differences of IT managerial and technical trends. Going beyond identifying these influential factors is also the need to understand the considerations for addressing them in light of recognizing the respective local characteristics, especially when operating in a globally linked environment, although somehow heavily influenced locally. By comparing and contrasting IT trends from different geographies, this paper presents important local and international factors (e.g., management concerns, influential technologies, budgets/spending, organizational considerations) necessary to prepare IT leaders for the challenges that await them. It can also serve as an indicator as the respective geographies evolve from the economic conundrum. The research is based on data from four geographic regions (United States (US), Europe, Asia, and Latin America). The same questionnaire (although translated for the respective respondents), based on the lead authors well-respected and long-running Society for Information Management survey, was applied across the geographies. This paper presents the major findings based on survey responses from 620 respondents (275 US, 100 European, 59 Asian, and 186 Latin) in mid-2011. The top five management concerns were: (1) IT and business alignment; (2) business agility and speed to market; (3) business process management and business process reengineering; (4) business productivity and cost reduction; (5) IT reliability and efficiency. The five most influential technologies were: (1) business intelligence; (2) enterprise resource planning systems; (3) cloud computing; (4) mobile and wireless applications; (5) customer relationship management.
Tumor radiation response enhancement by acoustical stimulation of the vasculature
Authors: Czarnota Gregory J. , Karshafian Raffi , Burns Peter N. , Wong Shun , Al Mahrouki Azza , Lee Justin W. , Caissie Amanda , Tran William , Kim Christina , Furukawa Melissa , Wong Emily , Giles Anoja
Published: July 2012

We have discovered that ultrasound-mediated microbubble vascular disruption can enhance tumor responses to radiation in vivo. We demonstrate this effect using a human PC3 prostate cancer xenograft model. Results indicate a synergistic effect in vivo with combined single treatments of ultrasound-stimulated microbubble vascular perturbation and radiation inducing an over 10-fold greater cell kill with combined treatments. We further demonstrate with experiments in vivo that induction of ceramide-related endothelial cell apoptosis, leading to vascular disruption, is a causative mechanism. In vivo experiments with ultrasound and bubbles permit radiation doses to be decreased significantly for comparable effect. We envisage this unique combined ultrasound-based vascular perturbation and radiation treatment method being used to enhance the effects of radiation in a tumor, leading to greater tumor eradication.
Antisense RNA that affects
Rhodopseudomonas palustris
quorum-sensing signal receptor expression
Authors: Hirakawa Hidetada , Harwood Caroline S. , Pechter Kieran B. , Schaefer Amy L. , Greenberg E. Peter
Published: July 2012

Quorum sensing in the bacterium
Rhodopseudomonas palustris
involves the RpaI signal synthase, which produces
p
-coumaroyl-homoserine lactone (
p
C-HSL) and RpaR, which is a
p
C-HSL–dependent transcriptional activator. There is also an antisense
rpaR
transcript (as
rpaR
) of unknown function. Recent RNAseq studies have revealed that bacterial antisense RNAs are abundant, but little is known about the function of these molecules. Because as
rpaR
expression is quorum sensing dependent, we sought to characterize its production and function. We show that as
rpaR
is approximately 300–600 bases and is produced in response to
p
C-HSL and RpaR. There is an RpaR-binding site centered 51.5 bp from the mapped as
rpaR
transcript start site. We show that as
rpaR
overexpression reduces RpaR levels,
rpaI
expression, and
p
C-HSL production. We also generated an as
rpaR
mutant, which shows elevated RpaR levels, and elevated
rpaI
expression. Thus, as
rpaR
inhibits
rpaR
translation, and this inhibition results in suppression of RpaR-dependent
rpaI
expression and, thus,
p
C-HSL production. The
R. palustris
as
rpaR
represents an antisense RNA for which an activity can be measured and for which a distinct regulatory circuit related to a function is elucidated. It also represents yet another subtle regulatory layer for acyl-homoserine lactone quorum-sensing signal-responsive transcription factors.
Remote control of renal physiology by the intestinal neuropeptide pigment-dispersing factor in
Drosophila
Authors: Talsma Aaron D. , Christov Christo P. , Terriente-Felix Ana , Linneweber Gerit A. , Perea Daniel , Wayland Matthew , Shafer Orie T. , Miguel-Aliaga Irene
Published: July 2012

The role of the central neuropeptide pigment-dispersing factor (PDF) in circadian timekeeping in
Drosophila
is remarkably similar to that of vasoactive intestinal peptide (VIP) in mammals. Like VIP, PDF is expressed outside the circadian network by neurons innervating the gut, but the function and mode of action of this PDF have not been characterized. Here we investigate the visceral roles of PDF by adapting cellular and physiological methods to the study of visceral responses to PDF signaling in wild-type and mutant genetic backgrounds. We find that intestinal PDF acts at a distance on the renal system, where it regulates ureter contractions. We show that PdfR, PDF's established receptor, is expressed by the muscles of the excretory system, and present evidence that PdfR-induced cAMP increases underlie the myotropic effects of PDF. These findings extend the similarities between PDF and VIP beyond their shared central role as circadian regulators, and uncover an unexpected endocrine mode of myotropic action for an intestinal neuropeptide on the renal system.
Brain dopamine and serotonin differ in regulation and its consequences
Authors: Hashemi Parastoo , Dankoski Elyse C. , Lama Rinchen , Wood Kevin M. , Takmakov Pavel , Wightman R. Mark
Published: July 2012

Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome.
Sushi domains confer distinct trafficking profiles on GABA
B
receptors
Authors: Hannan Saad , Wilkins Megan E. , Smart Trevor G.
Published: July 2012

GABA
B
receptors mediate slow inhibitory neurotransmission in the brain and feature during excitatory synaptic plasticity, as well as various neurological conditions. These receptors are obligate heterodimers composed of GABA
B
R1 and R2 subunits. The two predominant R1 isoforms differ by the presence of two complement control protein modules or Sushi domains (SDs) in the N terminus of R1a. By using live imaging, with an α-bungarotoxin-binding site (BBS) and fluorophore-linked bungarotoxin, we studied how R2 stabilizes R1b subunits at the cell surface. Heterodimerization with R2 reduced the rate of internalization of R1b, compared with R1b homomers. However, R1aR2 heteromers exhibited increased cell surface stability compared with R1bR2 receptors in hippocampal neurons, suggesting that for receptors containing the R1a subunit, the SDs play an additional role in the surface stability of GABA
B
receptors. Both SDs were necessary to increase the stability of R1aR2 because single deletions caused the receptors to be internalized at the same rate and extent as R1bR2 receptors. Consistent with these findings, a chimera formed from the metabotropic glutamate receptor (mGluR)2 and the SDs from R1a increased the surface stability of mGluR2. These results suggest a role for SDs in stabilizing cell surface receptors that could impart different pre- and postsynaptic trafficking itineraries on GABA
B
receptors, thereby contributing to their physiological and pathological roles.
Sensing and decision-making in random search
Authors: Hein Andrew M. , McKinley Scott A.
Published: July 2012

Many organisms locate resources in environments in which sensory signals are rare, noisy, and lack directional information. Recent studies of search in such environments model search behavior using random walks (e.g., Lévy walks) that match empirical movement distributions. We extend this modeling approach to include searcher responses to noisy sensory data. We explore the consequences of incorporating such sensory measurements into search behavior using simulations of a visual-olfactory predator in search of prey. Our results show that including even a simple response to noisy sensory data can dominate other features of random search, resulting in lower mean search times and decreased risk of long intervals between target encounters. In particular, we show that a lack of signal is not a lack of information. Searchers that receive no signal can quickly abandon target-poor regions. On the other hand, receiving a strong signal leads a searcher to concentrate search effort near targets. These responses cause simulated searchers to exhibit an emergent area-restricted search behavior similar to that observed of many organisms in nature.
Redox systematics of a magma ocean with variable pressure-temperature gradients and composition
Authors: Righter K. , Ghiorso M. S.
Published: July 2012

Oxygen fugacity in metal-bearing systems controls some fundamental aspects of the geochemistry of the early Earth, such as the FeO and siderophile trace element content of the mantle, volatile species that influence atmospheric composition, and conditions for organic compounds synthesis. Redox and metal-silicate equilibria in the early Earth are sensitive to oxygen fugacity (fO2), yet are poorly constrained in modeling and experimentation. High pressure and temperature experimentation and modeling in metal-silicate systems usually employs an approximation approach for estimating fO2that is based on the ratio of Fe and FeO [called “ΔIW (ratio)” hereafter]. We present a new approach that utilizes free energy and activity modeling of the equilibrium: Fe + SiO2 + O2 = Fe2SiO4to calculate absolute fO2and relative to the iron-wüstite (IW) buffer at pressure and temperature [ΔIW (P,T)]. This equilibrium is considered across a wide range of pressures and temperatures, including up to the liquidus temperature of peridotite (4,000 K at 50 GPa). Application of ΔIW (ratio) to metal-silicate experiments can be three or four orders of magnitude different from ΔIW (P,T) values calculated using free energy and activity modeling. We will also use this approach to consider the variation in oxygen fugacity in a magma ocean scenario for various thermal structures for the early Earth: hot liquidus gradient, 100 °C below the liquidus, hot and cool adiabatic gradients, and a cool subsolidus adiabat. The results are used to assess the effect of increasing P and T, changing silicate composition during accretion, and related to current models for accretion and core formation in the Earth. The fO2in a deep magma ocean scenario may become lower relative to the IW buffer at hotter and deeper conditions, which could include metal entrainment scenarios. Therefore, fO2may evolve from high to low fO2during Earth (and other differentiated bodies) accretion. Any modeling of core formation and metal-silicate equilibrium should take these effects into account.
Interleukin-1R3 mediates interleukin-1–induced potassium current increase through fast activation of Akt kinase
Authors: Qian Jiang , Zhu Ling , Li Qiming , Belevych Natalya , Chen Qun , Zhao Fangli , Herness Scott , Quan Ning
Published: July 2012

Inflammatory cytokine interleukin-1 (IL-1) performs multiple functions in the central nervous system. The type 1 IL-1 receptor (IL-1R1) and the IL-1 receptor accessory protein (IL-1RAcP) form a functional IL-1 receptor complex that is thought to mediate most, if not all, IL-1–induced effects. Several recent studies, however, suggest the existence of a heretofore-unidentified receptor for IL-1. In this study, we report that the IL-1R1 gene contains an internal promoter that drives the transcription of a shortened IL-1R1 mRNA. This mRNA is the template for a unique IL-1R protein that is identical to IL-1R1 at the C terminus, but with a shorter extracellular domain at the N terminus. We have termed this molecule IL-1R3. The mRNA and protein for IL-1R3 are expressed in normal and two strains of commercially available IL-1R1 knockout mice. Western blot analysis shows IL-1R3 is preferentially expressed in neural tissues. Furthermore, IL-1β binds specifically to IL-1R3 when it is complexed with the newly discovered alternative IL-1 receptor accessory protein, IL-1RAcPb. Stimulation of neurons expressing both IL-1R3 and IL-1RAcPb with IL-1β causes fast activation of the Akt kinase, which leads to an increase in voltage-gated potassium current. These results demonstrate that IL-1R3/IL-1RAcPb complex mediates a unique subset of IL-1 activity that accounts for many previously unexplained IL-1 effects in the central nervous system.
Preparation of unnatural N-to-N and C-to-C protein fusions
Authors: Witte Martin D. , Cragnolini Juan J. , Dougan Stephanie K. , Yoder Nicholas C. , Popp Maximilian W. , Ploegh Hidde L.
Published: July 2012

Standard genetic approaches allow the production of protein composites by fusion of polypeptides in head-to-tail fashion. Some applications would benefit from constructions that are genetically impossible, such as the site-specific linkage of proteins via their N or C termini, when a remaining free terminus is required for biological activity. We developed a method for the production of N-to-N and C-to-C dimers, with full retention of the biological activity of both fusion partners and without inflicting chemical damage on the proteins to be joined. We use sortase A to install on the N or C terminus of proteins of interest the requisite modifications to execute a strain-promoted copper-free cycloaddition and show that the ensuing ligation proceeds efficiently. Applied here to protein–protein fusions, the method reported can be extended to connecting proteins with any entity of interest.
Improving aerosol distributions below clouds by assimilating satellite-retrieved cloud droplet number
Authors: Saide Pablo E. , Carmichael Gregory R. , Spak Scott N. , Minnis Patrick , Ayers J. Kirk
Published: July 2012

Limitations in current capabilities to constrain aerosols adversely impact atmospheric simulations. Typically, aerosol burdens within models are constrained employing satellite aerosol optical properties, which are not available under cloudy conditions. Here we set the first steps to overcome the long-standing limitation that aerosols cannot be constrained using satellite remote sensing under cloudy conditions. We introduce a unique data assimilation method that uses cloud droplet number (Nd) retrievals to improve predicted below-cloud aerosol mass and number concentrations. The assimilation, which uses an adjoint aerosol activation parameterization, improves agreement with independentNdobservations and with in situ aerosol measurements below shallow cumulus clouds. The impacts of a single assimilation on aerosol and cloud forecasts extend beyond 24 h. Unlike previous methods, this technique can directly improve predictions of near-surface fine mode aerosols responsible for human health impacts and low-cloud radiative forcing. Better constrained aerosol distributions will help improve health effects studies, atmospheric emissions estimates, and air-quality, weather, and climate predictions.
Redox alters yellow dragonflies into red
Authors: Futahashi Ryo , Kurita Ryoji , Mano Hiroaki , Fukatsu Takema
Published: July 2012

Body color change associated with sexual maturation—so-called nuptial coloration—is commonly found in diverse vertebrates and invertebrates, and plays important roles for their reproductive success. In some dragonflies, whereas females and young males are yellowish in color, aged males turn vivid red upon sexual maturation. The male-specific coloration plays pivotal roles in, for example, mating and territoriality, but molecular basis of the sex-related transition in body coloration of the dragonflies has been poorly understood. Here we demonstrate that yellow/red color changes in the dragonflies are regulated by redox states of epidermal ommochrome pigments. Ratios of reduced-form pigments to oxidized-form pigments were significantly higher in red mature males than yellow females and immature males. The ommochrome pigments extracted from the dragonflies changed color according to redox conditions in vitro: from red to yellow in the presence of oxidant and from yellow to red in the presence of reductant. By injecting the reductant solution into live insects, the yellow-to-red color change was experimentally reproduced in vivo in immature males and mature females. Discontinuous yellow/red mosaicism was observed in body coloration of gynandromorphic dragonflies, suggesting a cell-autonomous regulation over the redox states of the ommochrome pigments. Our finding extends the mechanical repertoire of pigment-based body color change in animals, and highlights an impressively simple molecular mechanism that regulates an ecologically important color trait.
Compensatory mechanisms for ameliorating the fundamental trade-off between predator avoidance and foraging
Authors: Thaler Jennifer S. , McArt Scott H. , Kaplan Ian
Published: July 2012

Most organisms face the problem of foraging and maintaining growth while avoiding predators. Typical animal responses to predator exposure include reduced feeding, elevated metabolism, and altered development rate, all of which can be beneficial in the presence of predators but detrimental in their absence. How then do animals balance growth and predator avoidance? In a series of field and greenhouse experiments, we document that the tobacco hornworm caterpillar,Manduca sexta,reduced feeding by 30–40% owing to the risk of predation by stink bugs, but developed more rapidly and gained the same mass as unthreatened caterpillars. Assimilation efficiency, extraction of nitrogen from food, and percent body lipid content all increased during the initial phase (1-3 d) of predation risk, indicating that enhanced nutritional physiology allows caterpillars to compensate when threatened. However, we report physiological costs of predation risk, including altered body composition (decreased glycogen) and reductions in assimilation efficiency later in development. Our findings indicate that hornworm caterpillars use temporally dynamic compensatory mechanisms that ameliorate the trade-off between predator avoidance and growth in the short term, deferring costs to a period when they are less vulnerable to predation.
Characterization of two neuronal subclasses through constellation pharmacology
Authors: Teichert Russell W. , Raghuraman Shrinivasan , Memon Tosifa , Cox Jeffrey L. , Foulkes Tucker , Rivier Jean E. , Olivera Baldomero M.
Published: July 2012

Different types of neurons diverge in function because they express their own unique set or constellation of signaling molecules, including receptors and ion channels that work in concert. We describe an approach to identify functionally divergent neurons within a large, heterogeneous neuronal population while simultaneously investigating specific isoforms of signaling molecules expressed in each. In this study we characterized two subclasses of menthol-sensitive neurons from cultures of dissociated mouse dorsal-root ganglia. Although these neurons represent a small fraction of the dorsal-root ganglia neuronal population, we were able to identify them and investigate the cell-specific constellations of ion channels and receptors functionally expressed in each subclass, using a panel of selective pharmacological tools. Differences were found in the functional expression of ATP receptors, TRPA1 channels, voltage-gated calcium-, potassium-, and sodium channels, and responses to physiologically relevant cold temperatures. Furthermore, the cell-specific responses to various stimuli could be altered through pharmacological interventions targeted to the cell-specific constellation of ion channels expressed in each menthol-sensitive subclass. In fact, the normal responses to cold temperature could be reversed in the two neuronal subclasses by the coapplication of the appropriate combination of pharmacological agents. This result suggests that the functionally integrated constellation of signaling molecules in a particular type of cell is a more appropriate target for effective pharmacological intervention than a single signaling molecule. This shift from molecular to cellular targets has important implications for basic research and drug discovery. We refer to this paradigm as “constellation pharmacology.”
Circadian clock protein cryptochrome regulates the expression of proinflammatory cytokines
Authors: Narasimamurthy Rajesh , Hatori Megumi , Nayak Surendra K. , Liu Fei , Panda Satchidananda , Verma Inder M.
Published: July 2012

Chronic sleep deprivation perturbs the circadian clock and increases susceptibility to diseases such as diabetes, obesity, and cancer. Increased inflammation is one of the common underlying mechanisms of these diseases, thus raising a hypothesis that circadian-oscillator components may regulate immune response. Here we show that absence of the core clock component protein cryptochrome (CRY) leads to constitutive elevation of proinflammatory cytokines in a cell-autonomous manner. We observed a constitutive NF–κB and protein kinase A (PKA) signaling activation in

Cry1
−/−
;Cry2
−/−

cells. We further demonstrate that increased phosphorylation of p65 at S276 residue in

Cry1
−/−
;Cry2
−/−

cells is due to increased PKA signaling activity, likely induced by a significantly high basal level of cAMP, which we detected in these cells. In addition, we report that CRY1 binds to adenylyl cyclase and limits cAMP production. Based on these data, we propose that absence of CRY protein(s) might release its (their) inhibition on cAMP production, resulting in elevated cAMP and increased PKA activation, subsequently leading to NF–κB activation through phosphorylation of p65 at S276. These results offer a mechanistic framework for understanding the link between circadian rhythm disruption and increased susceptibility to chronic inflammatory diseases.
Using structural cues to guide readers on the internet
Authors: Spyridakis Jan H. , Mobrand Kathryn A. , Cuddihy Elisabeth , Wei Carolyn Y.
Published: July 2012

This paper reviews three studies that examined how users performance is affected by the (1) explicitness of local navigational links, (2) intriguing and informative phrasing of hyperlinks, and (3) text previews and navigational menus. The results reveal that sites with highly explicit navigational links increase site exploration as well as site perceptions; a mismatch between navigation and embedded link labels increases comprehension and site exploration; and previews with embedded links increase inferential comprehension, though they are disliked. We suggest a combined approach to structural cueing and emphasize that good design is context specific – designs that support comprehension do not necessarily receive high marks for usability.