Microscopic Analysis of Severe Structural Rearrangements of the Plant Endoplasmic Reticulum and Golgi Caused by Overexpression of Poa semilatent virus Movement Protein

Cell-to-cell transport of plant viruses is mediated by virus-encoded movement proteins and occurs through plasmodesmata interconnecting neighboring cells in plant tissues. Three movement proteins coded by the “triple gene block” (TGB) and named TGBp1, TGBp2 and TGBp3 have distinct functions in viral transport. TGBp1 binds viral genomic RNAs to form ribonucleoprotein complexes representing the transport form of viral genome, while TGBp2 and TGBp3 are necessary for intracellular delivery of such complexes to plasmodesmata. Recently, it was revealed that overexpression of Potato virus X TGBp3 triggers the unfolded protein response mitigating the endoplasmic reticulum (ER) stress leading to cell death if this protein reaches high levels in the ER. Here we report microscopic studies of the influence of the Poa semilatent hordeivirus TGBp3 overexpressed in Nicotiana benthamiana epidermal cells by particle bombardment on cell endomembranes and demonstrate that the protein C-terminal transmembrane segment contains a determinant responsible for vesiculation and coalescence of the endoplasmic reticulum and Golgi presumably accompanying the ER stress that can be induced upon high-level TGBp3 expression

Climatology of Tibetan Plateau Vortices in reanalysis data and a high-resolution global climate model

The Tibetan Plateau (TP) and surrounding high mountains constitute an important forcing of the atmospheric circulation due to their height and extent, and thereby impact weather and climate in downstream regions of East Asia. Mesoscale Tibetan Plateau Vortices (TPVs) are one of the major precipitation-producing systems on the TP. A fraction of TPVs moves off the TP to the east and can trigger extreme precipitation in parts of China, e.g. the Sichuan province and the Yangtze River valley, that can result in severe flooding. In this study, the climatology of TPV occurrence is examined in two reanalyses and, for the first time, in a high-resolution global climate model using an objective feature tracking algorithm. Most TPVs are generated in the north-western part of the TP; the centre of this main genesis region is small and stable throughout the year. The strength and position of the subtropical westerly jet is correlated to the distance TPVs can travel eastwards and therefore could have an effect on whether or not a TPV is moving-off the TP. TPV-associated precipitation can account for up to 40% of the total precipitation in parts of China in selected months, often due to individual TPVs. The results show that the global climate model is able to simulate TPVs at N512 (~25 km) horizontal resolution and in general agrees with the reanalyses. The fact that the global climate model can represent the TPV climatology opens a wide range of options for future model-based research on TPVs

Extended microsatellite analysis in microsatellite stable, MSH2 and MLH1 mutation-negative HNPCC patients: Genetic reclassification and correlation with clinical features

Background: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant disorder predisposing to predominantly colorectal cancer (CRC) and endometrial cancer frequently due to germline mutations in DNA mismatch repair (MMR) genes, mainly MLH1, MSH2 and also MSH6 in families seen to demonstrate an excess of endometrial cancer. As a consequence, tumors in HNPCC reveal alterations in the length of simple repetitive genomic sequences like poly-A, poly-T, CA or GT repeats (microsatellites) in at least 90% of the cases. Aim of the Study: The study cohort consisted of 25 HNPCC index patients ( 19 Amsterdam positive, 6 Bethesda positive) who revealed a microsatellite stable (MSS) - or low instable (MSI-L) - tumor phenotype with negative mutation analysis for the MMR genes MLH1 and MSH2. An extended marker panel (BAT40, D10S197, D13S153, D18S58, MYCL1) was analyzed for the tumors of these patients with regard to three aspects. First, to reconfirm the MSI-L phenotype found by the standard panel; second, to find minor MSIs which might point towards an MSH6 mutation, and third, to reconfirm the MSS status of hereditary tumors. The reconfirmation of the MSS status of tumors not caused by mutations in the MMR genes should allow one to define another entity of hereditary CRC. Their clinical features were compared with those of 150 patients with sporadic CRCs. Results: In this way, 17 MSS and 8 MSI-L tumors were reclassified as 5 MSS, 18 MSI-L and even 2 MSI-H ( high instability) tumors, the last being seen to demonstrate at least 4 instable markers out of 10. Among all family members, 87 malignancies were documented. The mean age of onset for CRCs was the lowest in the MSI-H-phenotyped patients with 40.5 +/- 4.9 years (vs. 47.0 +/- 14.6 and 49.8 +/- 11.9 years in MSI-L- and MSS-phenotyped patients, respectively). The percentage of CRC was the highest in families with MSS-phenotyped tumors (88%), followed by MSI-L-phenotyped ( 78%) and then by MSI-H-phenotyped (67%) tumors. MSS tumors were preferentially localized in the distal colon supposing a similar biologic behavior like sporadic CRC. MSH6 mutation analysis for the MSI-L and MSI-H patients revealed one truncating mutation for a patient initially with an MSS tumor, which was reclassified as MSI-L by analyzing the extended marker panel. Conclusion: Extended microsatellite analysis serves to evaluate the sensitivity of the reference panel for HNPCC detection and permits phenotype confirmation or upgrading. Additionally, it confirms the MSS status of hereditary CRCs not caused by the common mutations in the MMR genes and provides hints to another entity of hereditary CRC. Copyright (C) 2004 S. Karger AG, Basel

The Antitumorigenic Function of EGFR in Metastatic Breast Cancer is Regulated by Expression of Mig6

Numerous studies by our lab and others demonstrate that epidermal growth factor receptor (EGFR) plays critical roles in primary breast cancer (BC) initiation, growth and dissemination. However, clinical trials targeting EGFR function in BC have lead to disappointing results. In the current study we sought to identify the mechanisms responsible for this disparity by investigating the function of EGFR across the continuum of the metastatic cascade. We previously established that overexpression of EGFR is sufficient for formation of in situ primary tumors by otherwise nontransformed murine mammary gland cells. Induction of epithelial-mesenchymal transition (EMT) is sufficient to drive the metastasis of these EGFR-transformed tumors. Examining growth factor receptor expression across this and other models revealed a potent downregulation of EGFR through metastatic progression. Consistent with diminution of EGFR following EMT and metastasis EGF stimulation changes from a proliferative to an apoptotic response in in situ versus metastatic tumor cells, respectively. Furthermore, overexpression of EGFR in metastatic MDA-MB-231 BC cells promoted their antitumorigenic response to EGF in three dimensional (3D) metastatic outgrowth assays. In line with the paradoxical function of EGFR through EMT and metastasis we demonstrate that the EGFR inhibitory molecule, Mitogen Induced Gene-6 (Mig6), is tumor suppressive in in situ tumor cells. However, Mig6 expression is absolutely required for prevention of apoptosis and ultimate metastasis of MDA-MB-231 cells. Further understanding of the paradoxical function of EGFR between primary and metastatic tumors will be essential for application of its targeted molecular therapies in BC

Different Asian monsoon rainfall responses to idealised orography sensitivity experiments in the HadGEM3-GA6 and FGOALS-FAMIL global climate models

Recent work has shown the dominance of the Himalayas in supporting the Indian summer monsoon (ISM), perhaps by surface sensible heating along its southern slope and by mechanical blocking acting to separate moist tropical flow from drier mid-latitude air. Previous studies have also shown that Indian summer rainfall is largely unaffected in sensitivity experiments that remove only the Tibetan Plateau. However, given the large biases in simulating the monsoon in CMIP5 models, such results may be model dependent. This study investigates the impact of orographic forcing from the Tibetan Plateau, Himalayas and Iranian Plateau on the ISM and East Asian summer monsoons (EASM) in the UK Met Office HadGEM3-GA6 and China’s Institute of Atmospheric Physics FGOALS-FAMIL GCMs. The models chosen feature opposite-signed biases in their simulation of the ISM rainfall and circulation climatology. The changes to ISM and EASM circulation across the sensitivity experiments are similar in both models and consistent with previous studies. However, considerable differences exist in the rainfall responses over India and China, and in the detailed aspects such as onset and retreat dates. In particular, the models show opposing changes in Indian monsoon rainfall when the Himalaya and Tibetan Plateau orography are removed. Our results show that a multi-model approach, as suggested in the forthcoming Global Monsoon Model Intercomparison Project (GMMIP) associated with CMIP6, is needed to clarify the impact of orographic forcing on the Asian monsoon and to fully understand the implications of model systematic error

Subtropical westerly jet influence on occurrence of western disturbances and Tibetan plateau vortices

Western disturbances (WDs) are mid-to-upper-tropospheric mesoscale vortices, which typically propagate along the subtropical westerly jet stream and bring heavy rainfall to Pakistan and northern India during boreal winter. They are dynamically similar to Tibetan Plateau vortices (TPVs), which affect southwest China during spring and summer and emanate from the Tibetan Plateau. Here, we propose that their similarity implies the existence of a more general group of upper-tropospheric vortices featuring interactions with the orography of the Hindu Kush-Himalaya-Tibetan Plateau region. Using existing track databases for WDs and TPVs derived from ERA-Interim reanalysis, we show that their respective occurrence frequencies are highly anticorrelated with each other through the seasonal cycle, yet both are strongly correlated with jet latitude. Our findings imply that the incidence of hazards due to WDs and TPVs is correlated on intra- and interannual timescales, particularly through upper-level baroclinicity

Steady state behaviour in atomic three-level lambda and ladder systems with incoherent population pumping

The steady state in three-level lambda and ladder systems is studied. It is well-known that in a lambda system this steady state is the coherent population trapping state, independent of the presence of spontaneous emission. In contrast, the steady state in a ladder system is in general not stable against radiative decay and exhibits a minimum in the population of the ground state. It is shown that incoherent population pumping destroys the stability of the coherent population trapping state in the lambda system and suppresses a previously discovered sharp dip in the steady state response. In the ladder system the observed minimum disappears in the presence of an incoherent pump on the upper transition.Comment: 4 pages, RevTex, 5 figures, to appear in Phys. Rev.

Quantum Communication with Phantom Photons

We show that quantum information may be transferred between atoms in different locations by using ``phantom photons'': the atoms are coupled through electromagnetic fields, but the corresponding field modes do not have to be fully populated. In the case where atoms are placed inside optical cavities, errors in quantum information processing due to photon absorption inside the cavity are diminished in this way. This effect persists up to intercavity distances of about a meter for the current levels of cavity losses, and may be useful for distributed quantum computing.Comment: 6 pages RevTex, 4 eps figures included. Revised calculation with more details about mode structure calculation and the introduction of losse

Rachis brittleness in a hybrid–parent barley (Hordeum vulgare) breeding germplasm with different combinations at the non‐brittle rachis genes

Two dominant, closely linked and complementary genes, Btr1 and Btr2, control rachis brittleness in barley. Recessive mutations in any of these genes turn the fragile rachis (brittle) into a tough rachis phenotype (non‐brittle). The cross of parents with alternative mutations in the btr genes leads to a brittle F1 hybrid that presents grain retention problems. We evaluated rachis fragility through a mechanical test and under natural conditions, in F1 crosses with different compositions at the btr genes. Brittleness was significantly higher in Btr1btr1Btr2btr2 crosses compared to hybrids and inbred parents carrying one of the mutations (btr1btr1Btr2Btr2/Btr1Btr1btr2btr2). This fact could jeopardize the efficient harvest of hybrids bearing alternative mutations, reducing the choice of possible crosses for hybrid barley breeding and hindering the exploitation of potential heterotic patterns. Furthermore, non‐brittle hybrids showed higher brittleness than inbreds, suggesting the presence of other dominant factors affecting the trait. In conclusion, this work encourages a deeper study of the genetic control of the rachis brittleness trait and urges the consideration of rachis tenacity as a target for hybrid barley breeding.This work was supported by the Spanish Ministry of Economy, Industry and Competitiveness grants RFP2015 00006‐00‐00, and RTA2012‐00033‐C03‐02, and by the contract “Iberia region hybrid barley variety development and understanding effects of adaptation genes in hybrids,” between CSIC and Syngenta Crop Protection AG, which included funding for MFC PhD scholarship