The tomato Prf complex is a molecular trap for bacterial effectors based on Pto transphosphorylation

The bacteria Pseudomonas syringae is a pathogen of many crop species and one of the model pathogens for studying plant and bacterial arms race coevolution. In the current model, plants perceive bacteria pathogens via plasma membrane receptors, and recognition leads to the activation of general defenses. In turn, bacteria inject proteins called effectors into the plant cell to prevent the activation of immune responses. AvrPto and AvrPtoB are two such proteins that inhibit multiple plant kinases. The tomato plant has reacted to these effectors by the evolution of a cytoplasmic resistance complex. This complex is compromised of two proteins, Prf and Pto kinase, and is capable of recognizing the effector proteins. How the Pto kinase is able to avoid inhibition by the effector proteins is currently unknown. Our data shows how the tomato plant utilizes dimerization of resistance proteins to gain advantage over the faster evolving bacterial pathogen. Here we illustrate that oligomerisation of Prf brings into proximity two Pto kinases allowing them to avoid inhibition by the effectors by transphosphorylation and to activate immune responses

Chapter 3: Pathophysiology

The hallmark pathophysiologic feature of dilated cardiomyopathy is systolic dysfunction. Several pathogenetic mechanisms appear to be operative. These include increased hemodynamic overload, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Although beneficial in the early stages of heart failure, these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Genetic causes account for 30\u201340% of DCM and involve genes that encode a heterogeneous group of molecules that participate in force generation, force transmission, sarcomere integrity, cytoskeletal and nuclear architecture, electrolyte homeostasis, mitochondrial function, and transcription. Additional research will improve our understanding of the complex and longitudinal molecular changes that lead from gene mutation to clinical expressio

The role of input materials in shallow seismogenic slip and forearc plateau development: International Ocean Discovery Program Expedition 362 Preliminary Report Sumatra Seismogenic Zone

Drilling the input materials of the north Sumatran subduction zone, part of the 5000 km long Sunda subduction zone system and the origin of the Mw ∼9.2 earthquake and tsunami that devastated coastal communities around the Indian Ocean in 2004, was designed to groundtruth the material properties causing unexpectedly shallow seismogenic slip and a distinctive forearc prism structure. The intriguing seismogenic behavior and forearc structure are not well explained by existing models or by relationships observed at margins where seismogenic slip typically occurs farther landward. The input materials of the north Sumatran subduction zone are a distinctively thick (as thick as 4-5 km) succession of primarily Bengal-Nicobar Fan-related sediments. The correspondence between the 2004 rupture location and the overlying prism plateau, as well as evidence for a strengthened input section, suggest the input materials are key to driving the distinctive slip behavior and long-term forearc structure. During Expedition 362, two sites on the Indian oceanic plate ∼250 km southwest of the subduction zone, Sites U1480 and U1481, were drilled, cored, and logged to a maximum depth of 1500 meters below seafloor. The succession of sediment/rocks that will develop into the plate boundary detachment and will drive growth of the forearc were sampled, and their progressive mechanical, frictional, and hydrogeological property evolution will be analyzed through postcruise experimental and modeling studies. Large penetration depths with good core recovery and successful wireline logging in the challenging submarine fan materials will enable evaluation of the role of thick sedimentar y subduction zone input sections in driving shallow slip and amplifying earthquake and tsunami magnitudes, at the Sunda subduction zone and globally at other subduction zones where submarine fan-influenced sections are being subducted

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

A Strategy for the Proliferation of Ulva prolifera, Main Causative Species of Green Tides, with Formation of Sporangia by Fragmentation

Ulva prolifera, a common green seaweed, is one of the causative species of green tides that occurred frequently along the shores of Qingdao in 2008 and had detrimental effects on the preparations for the 2008 Beijing Olympic Games sailing competition, since more than 30 percent of the area of the games was invaded. In view of the rapid accumulation of the vast biomass of floating U. prolifera in green tides, we investigated the formation of sporangia in disks of different diameters excised from U. prolifera, changes of the photosynthetic properties of cells during sporangia formation, and development of spores. The results suggested that disks less than 1.00 mm in diameter were optimal for the formation of sporangia, but there was a small amount of spore release in these. The highest percentage of area of spore release occurred in disks that were 2.50 mm in diameter. In contrast, sporangia were formed only at the cut edges of larger disks (3.00 mm, 3.50 mm, and 4.00 mm in diameter). Additionally, the majority of spores liberated from the disks appeared vigorous and developed successfully into new individuals. These results implied that fragments of the appropriate size from the U. prolifera thalli broken by a variety of factors via producing spores gave rise to the rapid proliferation of the seaweed under field conditions, which may be one of the most important factors to the rapid accumulation of the vast biomass of U. prolifera in the green tide that occurred in Qingdao, 2008

Rapid Accumulation of CD14+CD11c+ Dendritic Cells in Gut Mucosa of Celiac Disease after in vivo Gluten Challenge

Of antigen-presenting cells (APCs) expressing HLA-DQ molecules in the celiac disease (CD) lesion, CD11c(+) dendritic cells (DCs) co-expressing the monocyte marker CD14 are increased, whereas other DC subsets (CD1c(+) or CD103(+)) and CD163(+)CD11c(-) macrophages are all decreased. It is unclear whether these changes result from chronic inflammation or whether they represent early events in the gluten response. We have addressed this in a model of in vivo gluten challenge.Treated HLA-DQ2(+) CD patients (n = 12) and HLA-DQ2(+) gluten-sensitive control subjects (n = 12) on a gluten-free diet (GFD) were orally challenged with gluten for three days. Duodenal biopsies obtained before and after gluten challenge were subjected to immunohistochemistry. Single cell digests of duodenal biopsies from healthy controls (n = 4), treated CD (n = 3) and untreated CD (n = 3) patients were analyzed by flow cytometry.In treated CD patients, the gluten challenge increased the density of CD14(+)CD11c(+) DCs, whereas the density of CD103(+)CD11c(+) DCs and CD163(+)CD11c(-) macrophages decreased, and the density of CD1c(+)CD11c(+) DCs remained unchanged. Most CD14(+)CD11c(+) DCs co-expressed CCR2. The density of neutrophils also increased in the challenged mucosa, but in most patients no architectural changes or increase of CD3(+) intraepithelial lymphocytes (IELs) were found. In control tissue no significant changes were observed.Rapid accumulation of CD14(+)CD11c(+) DCs is specific to CD and precedes changes in mucosal architecture, indicating that this DC subset may be directly involved in the immunopathology of the disease. The expression of CCR2 and CD14 on the accumulating CD11c(+) DCs indicates that these cells are newly recruited monocytes

Search for pair-produced long-lived neutral particles decaying to jets in the ATLAS hadronic calorimeter in ppcollisions at √s=8TeV

The ATLAS detector at the Large Hadron Collider at CERN is used to search for the decay of a scalar boson to a pair of long-lived particles, neutral under the Standard Model gauge group, in 20.3fb−1of data collected in proton–proton collisions at √s=8TeV. This search is sensitive to long-lived particles that decay to Standard Model particles producing jets at the outer edge of the ATLAS electromagnetic calorimeter or inside the hadronic calorimeter. No significant excess of events is observed. Limits are reported on the product of the scalar boson production cross section times branching ratio into long-lived neutral particles as a function of the proper lifetime of the particles. Limits are reported for boson masses from 100 GeVto 900 GeV, and a long-lived neutral particle mass from 10 GeVto 150 GeV

Histone H4 Lysine 12 Acetylation Regulates Telomeric Heterochromatin Plasticity in Saccharomyces cerevisiae

Recent studies have established that the highly condensed and transcriptionally silent heterochromatic domains in budding yeast are virtually dynamic structures. The underlying mechanisms for heterochromatin dynamics, however, remain obscure. In this study, we show that histones are dynamically acetylated on H4K12 at telomeric heterochromatin, and this acetylation regulates several of the dynamic telomere properties. Using a de novo heterochromatin formation assay, we surprisingly found that acetylated H4K12 survived the formation of telomeric heterochromatin. Consistently, the histone acetyltransferase complex NuA4 bound to silenced telomeric regions and acetylated H4K12. H4K12 acetylation prevented the over-accumulation of Sir proteins at telomeric heterochromatin and elimination of this acetylation caused defects in multiple telomere-related processes, including transcription, telomere replication, and recombination. Together, these data shed light on a potential histone acetylation mark within telomeric heterochromatin that contributes to telomere plasticity

Coexisting Cyclic Parthenogens Comprise a Holocene Species Flock in Eubosmina

Background: Mixed breeding systems with extended clonal phases and weak sexual recruitment are widespread in nature but often thought to impede the formation of discrete evolutionary clusters. Thus, cyclic parthenogens, such as cladocerans and rotifers, could be predisposed to ‘‘species problems’ ’ and a lack of discrete species. However, species flocks have been proposed for one cladoceran group, Eubosmina, where putative species are sympatric, and there is a detailed paleolimnological record indicating a Holocene age. These factors make the Eubosmina system suitable for testing the hypotheses that extended clonal phases and weak sexual recruitment inhibit speciation. Although common garden experiments have revealed a genetic component to the morphotypic variation, the evolutionary significance of the morphotypes remains controversial. Methodology/Principal Findings: In the present study, we tested the hypothesis of a single polymorphic species (i.e., mixing occurs but selection maintains genes for morphology) in four northern European lakes where the morphotypes coexist. Our evidence is based on nuclear DNA sequence, mitochondrial DNA sequence, and morphometric analysis of coexisting morphotypes. We found significant genetic differentiation, genealogical exclusivity, and morphometric differentiation for coexisting morphotypes. Conclusions: We conclude that the studied morphotypes represent a group of young species undergoing speciation wit

A Nation-Wide multicenter 10-year (1999-2008) retrospective clinical epidemiological study of female breast cancer in china

<p>Abstract</p> <p>Background</p> <p>According to the very limited cancer registry, incidence and mortality rates for female breast cancer in China are regarded to be increasing especially in the metropolitan areas. Representative data on the breast cancer profile of Chinese women and its time trend over years are relatively rare. The aims of the current study are to illustrate the breast cancer profile of Chinese women in time span and to explore the current treatment approaches to female breast cancer.</p> <p>Methods</p> <p>This was a hospital-based nation-wide and multi-center retrospective study of female primary breast cancer cases. China was divided into 7 regions according to the geographic distribution; from each region, one tertiary hospital was selected. With the exception of January and February, one month was randomly selected to represent each year from year 1999 to 2008 at every hospital. All inpatient cases within the selected month were reviewed and related information was collected based on the designed case report form (CRF). The Cancer Hospital/Institute, Chinese Academy of Medical Sciences (CICAMS) was the leading hospital in this study.</p> <p>Results</p> <p>Four-thousand two-hundred and eleven cases were randomly selected from the total pool of 45,200 patients and were included in the analysis. The mean age at diagnosis was 48.7 years (s.d. = 10.5 yrs) and breast cancer peaked in age group 40-49 yrs (38.6%). The most common subtype was infiltrating ductal carcinoma (86.5%). Clinical stage I & II accounted for 60.6% of 4,211 patients. Three-thousand five-hundred and thirty-four cases had estrogen receptor (ER) and progestin receptor (PR) tests, among them, 47.9% were positive for both. Two-thousand eight-hundred and forty-nine cases had human epidermal growth factor receptor 2(HER-2) tests, 25.8% of them were HER-2 positive. Among all treatment options, surgery (96.9% (4,078/4,211)) was predominant, followed by chemotherapy (81.4% (3,428/4,211). Much less patients underwent radiotherapy (22.6% (952/4,211)) and endocrine therapy (38.0% (1,599/4,211)).</p> <p>Conclusions</p> <p>The younger age of breast cancer onset among Chinese women and more advanced tumor stages pose a great challenge. Adjuvant therapy, especially radiotherapy and endocrine therapy are of great unmet needs.</p