bluuebunny/crossref_metadata_2025 huggingface dataset:
Chimpanzees as an animal model for human norovirus infection and vaccine development
Authors: Bok Karin , Parra Gabriel I. , Mitra Tanaji , Abente Eugenio , Shaver Charlene K. , Boon Denali , Engle Ronald , Yu Claro , Kapikian Albert Z. , Sosnovtsev Stanislav V. , Purcell Robert H. , Green Kim Y.
Published: December 2010

Noroviruses are global agents of acute gastroenteritis, but the development of control strategies has been hampered by the absence of a robust animal model. Studies in chimpanzees have played a key role in the characterization of several fastidious hepatitis viruses, and we investigated the feasibility of such studies for the noroviruses. Seronegative chimpanzees inoculated i.v. with the human norovirus strain Norwalk virus (NV) did not show clinical signs of gastroenteritis, but the onset and duration of virus shedding in stool and serum antibody responses were similar to that observed in humans. NV RNA was detected in intestinal and liver biopsies concurrent with the detection of viral shedding in stool, and NV antigen expression was observed in cells of the small intestinal lamina propria. Two infected chimpanzees rechallenged 4, 10, or 24 mo later with NV were resistant to reinfection, and the presence of NV-specific serum antibodies correlated with protection. We evaluated the immunogenicity and efficacy of virus-like particles (VLPs) derived from NV (genogroup I, GI) and MD145 (genogroup II, GII) noroviruses as vaccines. Chimpanzees vaccinated intramuscularly with GI VLPs were protected from NV infection when challenged 2 and 18 mo after vaccination, whereas chimpanzees that received GII VLPs vaccine or a placebo were not. This study establishes the chimpanzee as a viable animal model for the study of norovirus replication and immunity, and shows that NV VLP vaccines could induce protective homologous immunity even after extended periods of time.
Dual role of the receptor Tom20 in specificity and efficiency of protein import into mitochondria
Authors: Yamamoto Hayashi , Itoh Nobuka , Kawano Shin , Yatsukawa Yoh-ichi , Momose Takaki , Makio Tadashi , Matsunaga Mayumi , Yokota Mihoko , Esaki Masatoshi , Shodai Toshihiro , Kohda Daisuke , Aiken Hobbs Alyson E. , Jensen Robert E. , Endo Toshiya
Published: December 2010

Mitochondria import most of their resident proteins from the cytosol, and the import receptor Tom20 of the outer-membrane translocator TOM40 complex plays an essential role in specificity of mitochondrial protein import. Here we analyzed the effects of Tom20 binding on NMR spectra of a long mitochondrial presequence and found that it contains two distinct Tom20-binding elements. In vitro import and cross-linking experiments revealed that, although the N-terminal Tom20-binding element is essential for targeting to mitochondria, the C-terminal element increases efficiency of protein import in the step prior to translocation across the inner membrane. Therefore Tom20 has a dual role in protein import into mitochondria: recognition of the targeting signal in the presequence and tethering the presequence to the TOM40 complex to increase import efficiency.
Regulation of synaptic stability by AMPA receptor reverse signaling
Authors: Ripley Beth , Otto Stefanie , Tiglio Katie , Williams Megan E. , Ghosh Anirvan
Published: December 2010

The establishment of neuronal circuits relies on the stabilization of functionally appropriate connections and the elimination of inappropriate ones. Here we report that postsynaptic AMPA receptors play a critical role in regulating the stability of glutamatergic synapses. Removal of surface AMPA receptors leads to a decrease in the number and stability of excitatory presynaptic inputs, whereas overexpression increases synapse number and stability. Furthermore, overexpression of AMPA receptors along with Neuroligin-1 in 293T cells is sufficient to stabilize presynaptic inputs from cortical neurons onto heterologous cells. The stabilization of presynaptic inputs by AMPA receptors is not dependent on receptor-mediated current and instead relies on structural interactions mediated by the N-terminal domain of the glutamate receptor 2 (GluR2) subunit. These observations indicate that transsynaptic signaling mediated by the extracellular domain of GluR2 regulates the stability of presynaptic terminals.
Quantitative and empirical demonstration of the Matthew effect in a study of career longevity
Authors: Petersen Alexander M. , Jung Woo-Sung , Yang Jae-Suk , Stanley H. Eugene
Published: December 2010

The Matthew effect refers to the adage written some two-thousand years ago in the Gospel of St. Matthew: “For to all those who have, more will be given.” Even two millennia later, this idiom is used by sociologists to qualitatively describe the dynamics of individual progress and the interplay between status and reward. Quantitative studies of professional careers are traditionally limited by the difficulty in measuring progress and the lack of data on individual careers. However, in some professions, there are well-defined metrics that quantify career longevity, success, and prowess, which together contribute to the overall success rating for an individual employee. Here we demonstrate testable evidence of the age-old Matthew “
rich get richer
” effect, wherein the longevity and past success of an individual lead to a cumulative advantage in further developing his or her career. We develop an exactly solvable stochastic career progress model that quantitatively incorporates the Matthew effect and validate our model predictions for several competitive professions. We test our model on the careers of 400,000 scientists using data from six high-impact journals and further confirm our findings by testing the model on the careers of more than 20,000 athletes in four sports leagues. Our model highlights the importance of early career development, showing that many careers are stunted by the relative disadvantage associated with inexperience.
Single dose of anti–CTLA-4 enhances CD8
+
T-cell memory formation, function, and maintenance
Authors: Pedicord Virginia A. , Montalvo Welby , Leiner Ingrid M. , Allison James P.
Published: December 2010

CTLA-4, an Ig superfamily molecule with homology to CD28, is one of the most potent negative regulators of T-cell responses. In vivo blockade of CTLA-4 exacerbates autoimmunity, enhances tumor-specific T-cell responses, and may inhibit the induction of T-cell anergy. Clinical trials of CTLA-4–blocking antibodies to augment T-cell responses to malignant melanoma are at an advanced stage; however, little is known about the effects of CTLA-4 blockade on memory CD8
+
T-cell responses and the formation and maintenance of long-term CD8
+
T-cell memory. In our studies, we show that during in vivo memory CD8
+
T-cell responses to
Listeria monocytogenes
infection, CTLA-4 blockade enhances bacterial clearance and increases memory CD8
+
T-cell expansion. This is followed by an accumulation of memory cells that are capable of producing the effector cytokines IFN-γ and TNF-α. We also demonstrate that in a vaccination setting, blocking CTLA-4 during CD8
+
T-cell priming leads to increased expansion and maintenance of antigen-specific memory CD8
+
T cells without adversely affecting the overall T-cell repertoire. This leads to an increase in memory cell effector function and improved protective immunity against further bacterial challenges. These results indicate that transient blockade of CTLA-4 enhances memory CD8
+
T-cell responses and support the possible use of CTLA-4–blocking antibodies during vaccination to augment memory formation and maintenance.
C-X-C receptor type 4 promotes metastasis by activating p38 mitogen-activated protein kinase in myeloid differentiation antigen (Gr-1)-positive cells
Authors: Hiratsuka Sachie , Duda Dan G. , Huang Yuhui , Goel Shom , Sugiyama Tatsuki , Nagasawa Takashi , Fukumura Dai , Jain Rakesh K.
Published: December 2010

Increasing evidence suggests that myeloid bone marrow-derived cells (BMDCs) play a critical role in lung metastasis. Blockade of VEGF receptor 1 (VEGFR1) has been proposed as a potential strategy to limit myeloid BMDC recruitment to tumors. However, preclinical evidence indicates that this strategy may not be effective in all tumors. Thus, establishing which molecular mechanisms are responsible for the “escape” of these BMDCs from VEGFR1 inhibition would facilitate development of strategies to control metastasis. Here, we report the complementary role of the chemokine (C-X-C motif) ligand 12/C-X-C chemokine receptor 4 (CXCR4) and VEGF/VEGFR1 pathways in promoting lung metastasis in mice via BMDC recruitment using chimeric mice with deficiency in CXCR4 and VEGFR1–tyrosine kinase in the BMDCs. We first demonstrate that CXCR4 activity is essential for recruitment of myeloid differentiation antigen (Gr-1)-positive BMDCs, whereas VEGFR1 activity is responsible for macrophage recruitment in established tumors. Inhibition of both VEGFR1 and CXCR4 signaling in myeloid BMDCs exerted greater effects on tumor vascular density, growth, and lung metastasis than inhibition of VEGFR1 alone. These effects were reproduced after pharmacologic inhibition of CXCR4 with AMD3100. VEGFR1 and CXCR4 independently exerted a promigratory effect in myeloid BMDCs by activating p38 mitogen-activating protein kinase. Thus, combining CXCR4 blockade with inhibition of VEGFR1 may induce greater tumor growth delay and prevent or inhibit metastasis.
RNA editing enzyme adenosine deaminase is a restriction factor for controlling measles virus replication that also is required for embryogenesis
Authors: Ward Simone V. , George Cyril X. , Welch Megan J. , Liou Li-Ying , Hahm Bumsuk , Lewicki Hanna , de la Torre Juan C. , Samuel Charles E. , Oldstone Michael B.
Published: December 2010

Measles virus (MV), a member of the family Paramyxoviridae and an exclusively human pathogen, is among the most infectious viruses. A progressive fatal neurodegenerative complication, subacute sclerosing panencephalitis (SSPE), occurs during persistent MV infection of the CNS and is associated with biased hypermutations of the viral genome. The observed hypermutations of A-to-G are consistent with conversions catalyzed by the adenosine deaminase acting on RNA (ADAR1). To evaluate the role of ADAR1 in MV infection, we selectively disrupted expression of the IFN-inducible p150 ADAR1 isoform and found it caused embryonic lethality at embryo day (E) 11–E12. We therefore generated p150-deficient and WT mouse embryo fibroblast (MEF) cells stably expressing the MV receptor signaling lymphocyte activation molecule (SLAM or CD150). The p150
−/−
but not WT MEF cells displayed extensive syncytium formation and cytopathic effect (CPE) following infection with MV, consistent with an anti-MV role of the p150 isoform of ADAR1. MV titers were 3 to 4 log higher in p150
−/−
cells compared with WT cells at 21 h postinfection, and restoration of ADAR1 in p150
−/−
cells prevented MV cytopathology. In contrast to infection with MV, p150 disruption had no effect on vesicular stomatitis virus, reovirus, or lymphocytic choriomeningitis virus replication but protected against CPE resulting from infection with Newcastle disease virus, Sendai virus, canine distemper virus, and influenza A virus. Thus, ADAR1 is a restriction factor in the replication of paramyxoviruses and orthomyxoviruses.
Receptor-type guanylate cyclase is required for carbon dioxide sensation by
Caenorhabditis elegans
Authors: Hallem Elissa A. , Spencer W. Clay , McWhirter Rebecca D. , Zeller Georg , Henz Stefan R. , Rätsch Gunnar , Miller David M. , Horvitz H. Robert , Sternberg Paul W. , Ringstad Niels
Published: December 2010

CO
2
is both a critical regulator of animal physiology and an important sensory cue for many animals for host detection, food location, and mate finding. The free-living soil nematode
Caenorhabditis elegans
shows CO
2
avoidance behavior, which requires a pair of ciliated sensory neurons, the BAG neurons. Using in vivo calcium imaging, we show that CO
2
specifically activates the BAG neurons and that the CO
2
-sensing function of BAG neurons requires TAX-2/TAX-4 cyclic nucleotide-gated ion channels and the receptor-type guanylate cyclase GCY-9. Our results delineate a molecular pathway for CO
2
sensing and suggest that activation of a receptor-type guanylate cyclase is an evolutionarily conserved mechanism by which animals detect environmental CO
2
.
Both liver-X receptor (LXR) isoforms control energy expenditure by regulating Brown Adipose Tissue activity
Authors: Korach-André Marion , Archer Amena , Barros Rodrigo P. , Parini Paolo , Gustafsson Jan-Åke
Published: December 2010

Brown adipocytes are multilocular lipid storage cells that play a crucial role in nonshivering thermogenesis. Uncoupling protein 1 (UCP1) is a unique feature of brown fat cells that allows heat generation on sympathetic nervous system stimulation. As conventional transcriptional factors that are activated in various signaling pathways, liver-X receptors (LXRs) play important roles in many physiological processes. The role of LXRs in the regulation of energy homeostasis remains unclear, however. Female WT, LXRαβ
−/−
, LXRα
−/−
, and LXRβ
−/−
mice were fed with either a normal diet (ND) or a high-carbohydrate diet (HCD) supplemented with or without GW3965-LXR agonist. LXRαβ
−/−
mice exhibited higher energy expenditure (EE) as well as higher UCP1 expression in brown adipose tissue (BAT) compared with WT mice on the HCD. In addition, long-term treatment of WT mice with GW3965 showed lower EE at thermoneutrality (30 °C) and lower
Ucp1
expression level in BAT. Furthermore, H&E staining of the BAT of LXRαβ
−/−
mice exhibited decreased lipid droplet size compared with WT mice on the HCD associated with a more intense UCP1-positive reaction. Quantification of triglyceride (TG) content in BAT showed lower TG accumulation in LXRβ
−/−
mice compared with WT mice. Surprisingly, GW3965 treatment increased TG content (twofold) in the BAT of WT and LXRα
−/−
mice but not in LXRβ
−/−
mice. Furthermore, glucose transporter (GLUT4) in the BAT of LXRα
−/−
and LXRβ
−/−
mice was sixfold and fourfold increased, respectively, compared with WT mice on the ND. These findings suggest that LXRα as well as LXRβ could play a crucial role in the regulation of energy homeostasis in female mice and may be a potential target for the treatment of obesity and energy regulation.
Chk1 inhibits replication factory activation but allows dormant origin firing in existing factories
Authors: Ge Xin Quan , Blow J. Julian
Published: December 2010

Replication origins are licensed by loading MCM2-7 hexamers before entry into S phase. However, only ∼10% of licensed origins are normally used in S phase, with the others remaining dormant. When fork progression is inhibited, dormant origins initiate nearby to ensure that all of the DNA is eventually replicated. In apparent contrast, replicative stress activates ataxia telangiectasia and rad-3–related (ATR) and Chk1 checkpoint kinases that inhibit origin firing. In this study, we show that at low levels of replication stress, ATR/Chk1 predominantly suppresses origin initiation by inhibiting the activation of new replication factories, thereby reducing the number of active factories. At the same time, inhibition of replication fork progression allows dormant origins to initiate within existing replication factories. The inhibition of new factory activation by ATR/Chk1 therefore redirects replication toward active factories where forks are inhibited and away from regions that have yet to start replication. This minimizes the deleterious consequences of fork stalling and prevents similar problems from arising in unreplicated regions of the genome.
Zfp521 controls bone mass by HDAC3-dependent attenuation of Runx2 activity
Authors: Hesse Eric , Saito Hiroaki , Kiviranta Riku , Correa Diego , Yamana Kei , Neff Lynn , Toben Daniel , Duda Georg , Atfi Azeddine , Geoffroy Valérie , Horne William C. , Baron Roland
Published: December 2010

Runx2 is indispensable for osteoblast lineage commitment and early differentiation but also blocks osteoblast maturation, thereby causing bone loss in Runx2 transgenic mice. Zinc finger protein 521 (Zfp521) antagonizes Runx2 in vivo. Eliminating one Zfp521 allele mitigates the cleidocranial dysplasia–like phenotype of newborn Runx2+/− mice, whereas overexpressing Zfp521 exacerbates it. Overexpressing Zfp521 also reverses the severe osteopenia of adult Runx2 transgenic mice. Zfp521 binds to both Runx2 and histone deacetylase 3 (HDAC3), promotes their association, and antagonizes Runx2 transcriptional activity in an HDAC3-dependent manner. Mutating the Zfp521 zinc finger domains 6 and 26 reduces the binding of Zfp521 to Runx2 and inhibition of Runx2 activity. These data provide evidence that Zfp521 antagonizes Runx2 in vivo and thereby regulates two stages of osteoblast development, early during mesenchymal cell lineage commitment and later during osteoblast maturation. Thus, the balance and molecular interplay between Zfp521 and Runx2 contribute to the control of osteoblast differentiation, skeletal development, and bone homeostasis.
Microbiota-induced tertiary lymphoid tissues aggravate inflammatory disease in the absence of RORγt and LTi cells
Authors: Lochner Matthias , Ohnmacht Caspar , Presley Laura , Bruhns Pierre , Si-Tahar Mustapha , Sawa Shinichiro , Eberl Gérard
Published: December 2010

The programmed development of lymph nodes and Peyer’s patches during ontogeny requires lymphoid tissue inducer (LTi) cells that express the nuclear hormone receptor RORγt. After birth, LTi cells in the intestine cluster into cryptopatches, the precursors of isolated lymphoid follicles (ILFs), which are induced to form by symbiotic bacteria and maintain intestinal homeostasis. We show that in RORγt-deficient mice, which lack LTi cells, programmed lymphoid tissues, ILFs, and Th17 cells, bacterial containment requires the generation of large numbers of tertiary lymphoid tissues (tLTs) through the activity of B cells. However, upon epithelial damage, these mice develop severe intestinal inflammation characterized by extensive recruitment of neutrophils and IgG+ B cells, high expression of activation-induced deaminase in tLTs, and wasting disease. The pathology was prevented by antibiotic treatment or inhibition of lymphoid tissue formation and was significantly decreased by treatment with intravenous immunoglobulin G (IVIG). Our data show that intestinal immunodeficiency, such as an absence in RORγt-mediated proinflammatory immunity, can be compensated by increased lymphoid tissue genesis. However, this comes at a high cost for the host and can lead to a deregulated B cell response and aggravated inflammatory pathology.
IL-27 promotes T cell–dependent colitis through multiple mechanisms
Authors: Cox Jennifer H. , Kljavin Noelyn M. , Ramamoorthi Nandhini , Diehl Lauri , Batten Marcel , Ghilardi Nico
Published: December 2010

Interleukin-27 (IL-27) is a cytokine known to have both proinflammatory and immunoregulatory functions. The latter appear to dominate in vivo, where IL-27 suppresses TH17 responses and promotes the differentiation of Tr1 cells expressing interferon-γ and IL-10 and lacking forkhead box P3 (Foxp3). Accordingly, IL-27 receptor α (Il27ra)–deficient mice suffer from exacerbated immune pathology when infected with various parasites or challenged with autoantigens. Because the role of IL-27 in human and experimental mouse colitis is controversial, we studied the consequences of Il27ra deletion in the mouse T cell transfer model of colitis and unexpectedly discovered a proinflammatory role of IL-27. Absence of Il27ra on transferred T cells resulted in diminished weight loss and reduced colonic inflammation. A greater fraction of transferred T cells assumed a Foxp3+ phenotype in the absence of Il27ra, suggesting that IL-27 functions to restrain regulatory T cell (Treg) development. Indeed, IL-27 suppressed Foxp3 induction in vitro and in an ovalbumin-dependent tolerization model in vivo. Furthermore, effector cell proliferation and IFN-γ production were reduced in the absence of Il27ra. Collectively, we describe a proinflammatory role of IL-27 in T cell–dependent intestinal inflammation and provide a rationale for targeting this cytokine in pathological situations that result from a breakdown in peripheral immune tolerance.
Rapid expansion and long-term persistence of elevated NK cell numbers in humans infected with hantavirus
Authors: Björkström Niklas K. , Lindgren Therese , Stoltz Malin , Fauriat Cyril , Braun Monika , Evander Magnus , Michaëlsson Jakob , Malmberg Karl-Johan , Klingström Jonas , Ahlm Clas , Ljunggren Hans-Gustaf
Published: December 2010

Natural killer (NK) cells are known to mount a rapid response to several virus infections. In experimental models of acute viral infection, this response has been characterized by prompt NK cell activation and expansion followed by rapid contraction. In contrast to experimental model systems, much less is known about NK cell responses to acute viral infections in humans. We demonstrate that NK cells can rapidly expand and persist at highly elevated levels for >60 d after human hantavirus infection. A large part of the expanding NK cells expressed the activating receptor NKG2C and were functional in terms of expressing a licensing inhibitory killer cell immunoglobulin-like receptor (KIR) and ability to respond to target cell stimulation. These results demonstrate that NK cells can expand and remain elevated in numbers for a prolonged period of time in humans after a virus infection. In time, this response extends far beyond what is considered normal for an innate immune response.
Cyclophilin A is an inflammatory mediator that promotes atherosclerosis in apolipoprotein E–deficient mice
Authors: Nigro Patrizia , Satoh Kimio , O'Dell Michael R. , Soe Nwe Nwe , Cui Zhaoqiang , Mohan Amy , Abe Jun-ichi , Alexis Jeffrey D. , Sparks Janet D. , Berk Bradford C.
Published: December 2010

Cyclophilin A (CyPA; encoded by Ppia) is a ubiquitously expressed protein secreted in response to inflammatory stimuli. CyPA stimulates vascular smooth muscle cell migration and proliferation, endothelial cell adhesion molecule expression, and inflammatory cell chemotaxis. Given these activities, we hypothesized that CyPA would promote atherosclerosis. Apolipoprotein E–deficient (Apoe−/−) mice fed a high-cholesterol diet for 16 wk developed more severe atherosclerosis compared with Apoe−/−Ppia−/− mice. Moreover, CyPA deficiency was associated with decreased low-density lipoprotein uptake, VCAM-1 (vascular cell adhesion molecule 1) expression, apoptosis, and increased eNOS (endothelial nitric oxide synthase) expression. To understand the vascular role of CyPA in atherosclerosis development, bone marrow (BM) cell transplantation was performed. Atherosclerosis was greater in Apoe−/− mice compared with Apoe−/−Ppia−/− mice after reconstitution with CyPA+/+ BM cells, indicating that vascular-derived CyPA plays a crucial role in the progression of atherosclerosis. These data define a role for CyPA in atherosclerosis and suggest CyPA as a target for cardiovascular therapies.
Functional integration of a metabolic network model and expression data without arbitrary thresholding
Authors: Jensen Paul A. , Papin Jason A.
Published: December 2010

Motivation: Flux balance analysis (FBA) has been used extensively to analyze genome-scale, constraint-based models of metabolism in a variety of organisms. The predictive accuracy of such models has recently been improved through the integration of high-throughput expression profiles of metabolic genes and proteins. However, extensions of FBA often require that such data be discretized a priori into sets of genes or proteins that are either ‘on’ or ‘off’. This procedure requires selecting relatively subjective expression thresholds, often requiring several iterations and refinements to capture the expression dynamics and retain model functionality.

Results: We present a method for mapping expression data from a set of environmental, genetic or temporal conditions onto a metabolic network model without the need for arbitrary expression thresholds. Metabolic Adjustment by Differential Expression (MADE) uses the statistical significance of changes in gene or protein expression to create a functional metabolic model that most accurately recapitulates the expression dynamics. MADE was used to generate a series of models that reflect the metabolic adjustments seen in the transition from fermentative- to glycerol-based respiration in Saccharomyces cerevisiae. The calculated gene states match 98.7% of possible changes in expression, and the resulting models capture functional characteristics of the metabolic shift.

Availability: MADE is implemented in Matlab and requires a mixed-integer linear program solver. Source code is freely available at http://www.bme.virginia.edu/csbl/downloads/.

Contact:  papin@virginia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Statistical analysis of the cancer cell's molecular entropy using high-throughput data
Authors: van Wieringen Wessel N. , van der Vaart Aad W.
Published: December 2010

Motivation: As cancer progresses, DNA copy number aberrations accumulate and the genomic entropy (chromosomal disorganization) increases. For this surge to have any oncogenetic effect, it should (to some extent) be reflected at other molecular levels of the cancer cell, in particular that of the transcriptome. Such a coincidence of cancer progression and the propagation of an entropy increase through the molecular levels of the cancer cell would enhance the understanding of cancer evolution.

Results: A statistical argument reveals that (under some assumptions) an entropy increase in one random variable (DNA copy number) leads to an entropy increase in another (gene expression). Statistical methodology is provided to investigate the relation between the genomic and transcriptomic entropy using high-throughput data. Analyses of multiple high-throughput datasets using this methodology show a close, concordant relation among the genomic and transcriptomic entropy. Hence, as cancer evolves, and the genomic entropy increases, the transcriptomic entropy is also expected to surge.

Contact:  wvanwie@few.vu.nl

Supplementary information:  Supplementary data are available at Bioinformatics online.
Site-Specific Septoria Leaf Blotch Risk Assessment in Winter Wheat Using Weather-Radar Rainfall Estimates
Authors: Mahtour A. , El Jarroudi M. , Delobbe L. , Hoffmann L. , Maraite H. , Tychon B.
Published: December 2010

The Septoria leaf blotch prediction model PROCULTURE was used to assess the impact on simulated infection rates when using rainfall estimated by radar instead of rain gauge measurements. When comparing infection events simulated by PROCULTURE using radar- and gauge-derived data, the simulated probability of detection (POD) of infection events was high (0.83 on average), and the simulated false alarm ratio (FAR) of infection events was not negligible (0.24 on average). For most stations, simulation-observed FAR decreased to 0 and simulation-observed POD increased (0.85 on average) when the model outputs for both datasets were compared against visual observations of disease symptoms. An analysis of 148 infection events over 3 years at four locations showed no significant difference in the number of infection events of simulations using either dataset, indicating that, for a given location, radar estimates were as reliable as rain gauges for predicting infection events. Radar also provided better estimates of rainfall occurrence over a continuous space than weather station networks. The high spatial resolution provides radar with an important advantage that could significantly improve existing warning systems.
Occurrence of Chilli veinal mottle virus in Nicotiana tabacum in Yunnan, China
Authors: Ding M. , Yang C. , Zhang L. , Jiang Z.-L. , Fang Q. , Qin X.-Y. , Zhang Z.-K.
Published: December 2010

Flue-cured tobacco (Nicotiana tabacum) is an important crop in Yunnan Province, China. During a survey in July 2010, tobacco plants (N. tabacum cv. Yunyan 85) in the fields near Dali County in the northwest Yunnan Province of China had symptoms of chlorosis along leaf veins and later showed symptoms of white or brown necrosis along the veins. In 10 surveyed fields in Baizhishu Village in the city of Weishan, a commercial tobacco field (10 ha) developed virus-like disease symptoms; the incidence of affected plants ranged from 0.5 to 3%, which caused obvious economic losses. An isolate (YN75) was collected at random from five symptomatic leaves sampled from five plants. Negative staining of crude extracts of the infected leaves and subsequent electron microscopy revealed flexuous rods of 12 to 13 × 750 nm. Pinwheel-like inclusion bodies were abundant in thin sections of infected leaves. The particle size suggested a species of Potyviridae. Thus, the isolate was assayed in double antibody sandwich-ELISA (Agdia, Elkhart, IN) for the presence of Potato virus Y, Tobacco etch virus, and Tobacco vein mottling virus. All antigens gave negative results. Total RNA was extracted from leaves and tested by reverse transcription (RT)-PCR. The primer M4-T (5′-GTT TTC CCA GTC ACG ACT TTT TTT TTT TTT TT-3′) was employed for cDNA synthesis described by Chen et al (1). The primer set ChiVMV-F (5′-TAG TTG YGC ATA C (C/G) C AGG AGA GAG-3′)/M4 (5′-GTT TTC CCA GTC ACG AC-3′) is complimentary to the region of coat protein and 3′-untranslated region of Chilli veinal mottle virus (ChiVMV), respectively. The expected 1,189-bp fragments were amplified from RNA templates and the amplicon was cloned and sequenced (GenBank Accession No. HQ218936). Comparisons of amplicons with the amino acid sequence available in the NCBI database using BLAST showed 91.4% identity with ChiVMV from India (GenBank Accession No. EF213688) and 90.7% with ChiVMV from Taiwan (Accession No. DQ854950). The virus particle size, RT-PCR results, and sequence data revealed that these tobacco plants were infected by ChiVMV. To our knowledge, this is the first report of ChiVMV infecting N. tabacum in China.

Reference: (1) J. Chen et al. Arch. Virol. 146:757, 2001.
First Report of Orange Rust of Sugarcane Caused by Puccinia kuehnii in Ivory Coast and Cameroon
Authors: Saumtally A. S. , Viremouneix T. R. , Ahondokpê B. , Girard J-C. R. , Castlebury L. A. , Dixon L. , Glynn N. C. , Comstock J. C.
Published: December 2010

Orange rust of sugarcane caused by Puccinia kuehnii was detected in Florida in 2007 (1). It was hypothesized that the pathogen originated from Africa because brown rust of sugarcane (synonym common rust) was introduced to the Western Hemisphere from Africa (3). Requests for rust-infected sugarcane samples were made to several western and central African countries to investigate if orange rust of sugarcane was present but as yet undetected. Orange rust had not previously been reported from western or central Africa. At Zuénoula, Ivory Coast in July 2009, symptoms of sugarcane rust were observed on cvs. SP 71-6180 and Co 997 and appeared distinct to those of brown rust of sugarcane. A year later (May 2010), rust-infected specimens of SP 71-6180 and Co 997 from the same location and also from Borotou in Ivory Coast were sent to the USDA-ARS Systematic Mycology and Microbiology Laboratory in Beltsville, MD for identification. Also in May 2010, sugarcane rust was observed at Mbandjock and Nkoteng in Cameroon on cvs. D 88172, FR 87482, and RB 72-454 and on breeding clones RCmr 08/319 and RCmr 08/1121. All specimens had orange uredinial lesions that ranged from 0.6 to 6.5 mm × 200 to 300 μm and were ellipsoidal to elongate. Urediniospores were consistent with P. kuehnii E.J. Butler observed on specimens from Florida (1). DNA isolated from all samples was successfully amplified with P. kuehnii specific primers targeting ITS1 of rDNA (2). The nuclear large subunit region of rDNA of the rust specimens from Ivory Coast (BPI 881015–881017, GenBank Accession No. HQ666888) and Cameroon (BPI 881010–881014, GenBank Accession Nos. HQ666889–HQ666891) were sequenced. DNA sequences for all were identical to sequences of P. kuehnii and distinct from known sequences of P. melanocephala available in GenBank. To our knowledge, this is the first confirmed report of orange rust of sugarcane in western and central Africa. There is evidence that brown rust of sugarcane was introduced to the Western Hemisphere from this region of Africa (3) making it also the likely source of introduction of orange rust. Further experimentation is required to confirm this hypothesis.

References: (1) J. C. Comstock et al. Plant Dis. 92:175, 2008. (2) N. C. Glynn et al. Plant Pathol. 59:703. 2010. (3) H. L. Purdy et al. Plant Dis. 69:689, 1985.
First Report of Anthracnose Caused by Glomerella acutata on Chili Pepper in China
Authors: Xia H. , Wang X.-L. , Zhu H.-J. , Gao B.-D.
Published: December 2010

A new anthracnose disease on chili pepper (cayenne pepper cv. Hongxiu 2003, fruiting type pepper) was found in Zhijiang County, Hunan, China in 2009. The disease was observed only on the fruits. Lesions were generally elongated, on which dark acervuli were arranged concentrically. Later, cracking of older lesions was observed. With a microscope, fungal conidia were observed to be 15.8 × 4.1 μm, fusiform or oval with one end acute, and single celled with two to seven oil globules. No setae were found on the acervuli. Eight isolates (HNZJ001–HNZJ008) showed no difference in colony feature when cultured on potato dextrose agar. All the isolates showed white growth at the early stages, but colonies turned pink when they produced powdery spores and then finally became red gray. The average colony diameter was 68.5 to 72.3 mm after 7 days with obvious gray black concentric rings because of the development of aerial and substrate mycelia. After a needle-prick inoculation with a suspension of 1 × 106 spores per ml of HNZJ001 on 30 chili pepper fruits with three repeats, the same symptoms were observed and the same fungus was recovered. In bioassays, HNZJ001 caused lesions on both mature and immature fruits, while Glomerella cingulata strain LSQ1 (GenBank Accession No. HQ607386) used as a control did not infect immature fruits. PCR amplification was carried out by utilizing universal rDNA-ITS primer pair ITS4/ITS5. Sequencing of the PCR products of HNZJ001 (GenBank Accession No. GU059863) showed 100% identity to G. acutata (GenBank Accession No. EU008863) and Colletotrichum acutatum (GenBank Accession No. AF207794) after a BLAST search. The pathogen was identified as G. acutata (asexual stage: C. acutatum) on the basis of morphological characters and rDNA-ITS sequence analysis. Worldwide, it has been reported that pepper anthracnose might be caused by up to five species of Glomerella (Colletotrichum): G. cingulata, C. coccodes, C. capsici, C. dematium, and G. acutata (2), among which only the first three were previously reported in China. In recent years, G. acutata was reported on such plants as apple (3) and strawberry (1) in China, but not on pepper. To our knowledge, this is the first report of G. acutata on chili pepper in China.

References: (1) X.-J. Ren et al. Acta Phytopathol. Sin. 38:325, 2008. (2) P. P. Than et al. Zhejiang Univ. Sci. B 9:764, 2008. (3) R. Zhang et al. Plant Dis. 92:1474, 2008.
The Role of Arabidopsis Rubisco Activase in Jasmonate-Induced Leaf Senescence
Authors: Shan Xiaoyi , Wang Junxia , Chua Lingling , Jiang Dean , Peng Wen , Xie Daoxin
Published: December 2010

Leaf senescence, as the last stage of leaf development, is regulated by diverse developmental and environmental factors. Jasmonates (JAs) have been shown to induce leaf senescence in several plant species; however, the molecular mechanism for JA-induced leaf senescence remains unknown. In this study, proteomic, genetic, and physiological approaches were used to reveal the molecular basis of JA-induced leaf senescence in Arabidopsis (Arabidopsis thaliana). We identified 35 coronatine-insensitive 1 (COI1)-dependent JA-regulated proteins using two-dimensional difference gel electrophoresis in Arabidopsis. Among these 35 proteins, Rubisco activase (RCA) was a COI1-dependent JA-repressed protein. We found that RCA was down-regulated at the levels of transcript and protein abundance by JA in a COI1-dependent manner. We further found that loss of RCA led to typical senescence-associated features and that the COI1-dependent JA repression of RCA played an important role in JA-induced leaf senescence.
Arabidopsis Homologs of thePetunia HAIRY MERISTEMGene Are Required for Maintenance of Shoot and Root Indeterminacy
Authors: Engstrom Eric M. , Andersen Carl M. , Gumulak-Smith Juliann , Hu John , Orlova Evguenia , Sozzani Rosangela , Bowman John L.
Published: December 2010

Maintenance of indeterminacy is fundamental to the generation of plant architecture and a central component of the plant life strategy. Indeterminacy in plants is a characteristic of shoot and root meristems, which must balance maintenance of indeterminacy with organogenesis. The Petunia hybrida  HAIRY  MERISTEM (HAM) gene, a member of the GRAS family of transcriptional regulators, promotes shoot indeterminacy by an undefined non-cell-autonomous signaling mechanism(s). Here, we report that Arabidopsis (Arabidopsis thaliana) mutants triply homozygous for knockout alleles in three Arabidopsis HAM orthologs (Atham1,2,3 mutants) exhibit loss of indeterminacy in both the shoot and root. In the shoot, the degree of penetrance of the loss-of-indeterminacy phenotype of Atham1,2,3 mutants varies among shoot systems, with arrest of the primary vegetative shoot meristem occurring rarely or never, secondary shoot meristems typically arresting prior to initiating organogenesis, and inflorescence and flower meristems exhibiting a phenotypic range extending from wild type (flowers) to meristem arrest preempting organogenesis (flowers and inflorescence). Atham1,2,3 mutants also exhibit aberrant shoot phyllotaxis, lateral organ abnormalities, and altered meristem morphology in functioning meristems of both rosette and inflorescence. Root meristems of Atham1,2,3 mutants are significantly smaller than in the wild type in both longitudinal and radial axes, a consequence of reduced rates of meristem cell division that culminate in root meristem arrest. Atham1,2,3 phenotypes are unlikely to reflect complete loss of HAM function, as a fourth, more distantly related Arabidopsis HAM homolog, AtHAM4, exhibits overlapping function with AtHAM1 and AtHAM2 in promoting shoot indeterminacy.
iTRAQ Protein Profile Analysis of Arabidopsis Roots Reveals New Aspects Critical for Iron Homeostasis
Authors: Lan Ping , Li Wenfeng , Wen Tuan-Nan , Shiau Jeng-Yuan , Wu Yu-Ching , Lin Wendar , Schmidt Wolfgang
Published: December 2010

Iron (Fe) deficiency is a major constraint for plant growth and affects the quality of edible plant parts. To investigate the mechanisms underlying Fe homeostasis in plants, Fe deficiency-induced changes in the protein profile of Arabidopsis (Arabidopsis thaliana) roots were comprehensively analyzed using iTRAQ (Isobaric Tag for Relative and Absolute Quantification) differential liquid chromatography-tandem mass spectrometry on a LTQ-Orbitrap with high-energy collision dissociation. A total of 4,454 proteins were identified with a false discovery rate of less than 1.1%, and 2,882 were reliably quantified. A subset of 101 proteins was differentially expressed upon Fe deficiency. The changes in protein profiles upon Fe deficiency show low congruency with previously reported alterations in transcript levels, indicating posttranscriptional changes, and provide complementary information on Fe deficiency-induced processes. The abundance of proteins involved in the synthesis/regeneration of S-adenosylmethionine, the phenylpropanoid pathway, the response to oxidative stress, and respiration was highly increased by Fe deficiency. Using Fe-responsive proteins as bait, genome-wide fishing for partners with predictable or confirmed interologs revealed that RNA processing and ribonucleoprotein complex assembly may represent critical processes that contribute to the regulation of root responses to Fe deficiency, possibly by biasing translation efficiency.
Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells
Authors: Lee Sang‐Hun , Soltesz Ivan
Published: December 2010

Non technical summary  Cholecystokinin (CCK) is a widely expressed neuropeptide known to play key roles in both normal behaviour and pathophysiological conditions. Previous reports suggested that CCK serves as a unique molecular switch that differentially regulates the output of distinct types of inhibitory interneurons in the hippocampus. The current study focused on the underlying mechanisms of the CCK actions on hippocampal interneurons, and the results show that CCK modulates transmitter release from a major class of interneurons through cannabinoid type‐1 receptor signalling mechanisms. Taken together, the present data will help us better understand how CCK modulates neuronal circuits in the brain.
Requirements for synaptically evoked plateau potentials in relay cells of the dorsal lateral geniculate nucleus of the mouse
Authors: Dilger Emily K. , Shin Hee‐Sup , Guido William
Published: December 2010

Non‐technical summary In the developing visual system, spontaneous retinal activity plays an important role in the refinement of retinal ganglion cell projections to the dorsal lateral geniculate nucleus (dLGN) of thalamus. How such changes are implemented remains unknown. Recordings of post‐synaptic dLGN cell activity suggest that plateau‐like, L‐type Ca2+ channel‐mediated depolarizations figure prominently in remodelling. Plateaus are developmentally regulated and their incidence is controlled by the changing patterns of excitatory and inhibitory connections onto dLGN cells. At early ages there is a high degree of retinal convergence, and excitatory post‐synaptic events summate to produce depolarizations sufficient to activate plateaus. As these excitatory inputs are pruned and inhibitory connections emerge, the net excitatory drive is reduced and plateaus wane. Additionally, L‐type channels are highly expressed at young ages, and subunit disruptions resulting in decreased expression also affect the incidence of plateaus. These studies help elucidate the mechanisms underlying activity‐dependent refinement of sensory connections.
Automatic 3D Spiral Toolpath Generation for Single Point Incremental Forming
Authors: Malhotra Rajiv , Reddy N. V. , Cao Jian
Published: December 2010

Incremental forming (IF) of sheet metal is emerging as a useful flexible manufacturing process for forming customized shapes, some of which may not be formable using conventional techniques due to limitations of tooling or forming limit. In IF, the toolpath has a significant impact on the geometric accuracy, surface finish, and forming time of the formed component. Toolpath generation techniques used until date are based on commercial CAM packages (Skjoedt et al., 2007, “Creating 3D Spiral Tool Paths for Single Point Incremental Forming,” Key Eng. Mater., 344, pp. 583–590; Verbert et al., 2007, “Feature Based Approach for Increasing the Accuracy of the SPIF Process,” Key Eng. Mater., 344, pp. 527–534) and do not allow the generation of 3D spiral toolpaths for freeform components with constraints on both surface finish and geometric accuracy while simultaneously minimizing forming time. This work exploits the similarities between incremental forming and layered manufacturing to develop a methodology for automatic generation of 3D spiral single point incremental forming toolpaths for forming symmetric and asymmetric components, considering specified constraints on desired geometric accuracy and maximum specified scallop height while reducing the forming time. To test the developed methodology, the scallop heights of components formed using the developed methodology are measured and compared with the maximum permissible scallop heights specified. Furthermore, the geometric accuracy and forming time of the components formed using the developed methodology and by the toolpaths generated using commercial CAM software are compared. It is shown that the toolpaths generated using the developed methodology form components with better or similar geometric accuracy as compared with that generated by commercial CAM packages and with scallop heights lesser than the maximum permissible scallop height specified by the user. At the same time, the developed methodology also reduces the forming time as compared with commercial CAM toolpaths. This methodology can handle symmetric as well as asymmetric shapes and is a critical step toward automation of the toolpath generation for incremental forming.
Forming Limit and Fracture Mode of Microscale Laser Dynamic Forming
Authors: Li Ji , Gao Huang , Cheng Gary J.
Published: December 2010

The microscale laser dynamic forming (LDF) process is a high strain rate microfabrication technique, which uses a pulse laser to generate high pressure by vaporizing and ionizing an ablative coating, and thus produces complex 3D microstructures in thin foils. One of the most important features of this technique is ultrahigh strain rate (typically 106–7 s−1), which is theoretically favorable for increasing formability. However, due to the lack of measurement techniques in microscale and submicroscale, the formability of workpieces in LDF is hardly studied. In this article, experiments were carried out on aluminum foils to study the forming limits and fracture of thin films in LDF. The deformation depth was measured by an optical profilometer and the formed feature was observed using a focused ion beam and a scanning electron microscope. Meanwhile, a finite element model based on a modified Johnson–Cook constitutive model and a Johnson–Cook failure model was developed to simulate the mechanical and fracture behaviors of materials in LDF. Experimental results were used to verify the model. The verified model was used to predict the forming limit diagram of aluminum foil in LDF. The forming limit diagrams show a significant increase in formability compared with other metal forming processes.
Direct Three-Dimensional Layer Metal Deposition
Authors: Ruan Jianzhong , Tang Lie , Liou Frank W. , Landers Robert G.
Published: December 2010

Multi-axis slicing for solid freeform fabrication manufacturing processes can yield nonuniform thickness layers or three-dimensional (3D) layers. The traditional parallel layer construction approach to building such layers leads to the so-called staircase effect, which requires machining or other postprocessing to form the desired shape. This paper presents a direct 3D layer deposition approach that uses an empirical model to predict the layer thickness. The toolpath between layers is not parallel; instead, it follows the final shape of the designed geometry and the distance between the toolpath in the adjacent layers varies at different locations. Directly depositing 3D layers not only eliminates the staircase effect but also improves manufacturing efficiency by shortening the deposition and machining times. Simulation and experimental studies are conducted that demonstrate these advantages. Thus, the 3D deposition method is a beneficial addition to the traditional parallel deposition method.