In this paper, we address the joint target parameter estimation, range and Doppler frequency, in uniform linear array (ULA) multiple-input multiple-output (MIMO) radars. Cramér-Rao Lower Bounds ...(CRLB) bounds are obtained for the range and velocity of a target embedded in Complex Elliptically Symmetric (CES) distributed clutter with a specific focus on Complex t-distributed clutter. Numerical results are presented for the estimation performance in spiky clutter.
Extracellular matrix (ECM) degradation is a critical process in tumor cell invasion and requires matrix degrading protrusions called invadopodia. The Na(+)/H(+) exchanger (NHE1) has recently been ...shown to be fundamental in the regulation of invadopodia actin cytoskeleton dynamics and activity. However, the structural link between the invadopodia cytoskeleton and NHE1 is still unknown. A candidate could be ezrin, a linker between the NHE1 and the actin cytoskeleton known to play a pivotal role in invasion and metastasis. However, the mechanistic basis for its role remains unknown. Here, we demonstrate that ezrin phosphorylated at T567 is highly overexpressed in the membrane of human breast tumors and positively associated with invasive growth and HER2 overexpression. Further, in the metastatic cell line, MDA-MB-231, p-ezrin was almost exclusively expressed in invadopodia lipid rafts where it co-localized in a functional complex with NHE1, EGFR, ß1-integrin and phosphorylated-NHERF1. Manipulation by mutation of ezrins T567 phosphorylation state and/or PIP2 binding capacity or of NHE1s binding to ezrin or PIP2 demonstrated that p-ezrin expression and binding to PIP2 are required for invadopodia-mediated ECM degradation and invasion and identified NHE1 as the membrane protein that p-ezrin regulates to induce invadopodia formation and activity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cadmium is one of the most widespread pollutant in both terrestrial and marine environment, and its inhibitory effect on plant growth has been largely demonstrated. However, the molecular mechanisms ...underlying Cd toxicity in plant and mainly in root, as the first organ sensing soil heavy metals, need to be better investigated. To this aim, in the present work we analyzed the growth and the organization of
primary root in seedlings exposed to Cd (25 and 50 μM) for 8 days starting from germination. Root length, root meristem size, and organization were evaluated together with the behavior of some of the major molecular players in root growth and patterning. In particular, by using different GFP transgenic lines, we monitored: (i) the expression pattern of WOX5 and SCR transcription factors involved in the establishment and maintenance of stem cell niche and in the control of meristem size; (ii) the expression pattern of the IAA-inducible
reporter, PIN 1, 2, 3, 7 auxin carriers and
cytokinin-sensitive sensor as relevant components of hormone circuit controlling root growth. We report that Cd exposure inhibits primary root growth via affecting RAM stem cell niche and root radial pattern. At the molecular level, an impairment of auxin maximum accumulation at the root tip, related to a down-regulation and mislocalisation of PIN proteins, and an enhancement of
cytokinin-sensitive sensor signal is also detected under Cd treatment, thus suggesting an alteration in the homeostasis of auxin/cytokinin signaling. Moreover, and for the first time Cd toxicity on root growth and pattern has been related to a misexpression of SCR transcription factors which is known to interplay with auxin/cytokinin cross-talk in the control of RAM maintenance and activity.
Cancer cells have an unusual regulation of hydrogen ion dynamics that are driven by poor vascularity perfusion, regional hypoxia, and increased glycolysis. All these forces synergize/orchestrate ...together to create extracellular acidity and intracellular alkalinity. Precisely, they lead to extracellular pH (pH
) values as low as 6.2 and intracellular pH values as high as 8. This unique pH gradient (∆pH
to ∆pH
) across the cell membrane increases as the tumor progresses, and is markedly displaced from the electrochemical equilibrium of protons. These unusual pH dynamics influence cancer cell biology, including proliferation, metastasis, and metabolic adaptation. Warburg metabolism with increased glycolysis, even in the presence of Oxygen with the subsequent reduction in Krebs' cycle, is a common feature of most cancers. This metabolic reprogramming confers evolutionary advantages to cancer cells by enhancing their resistance to hypoxia, to chemotherapy or radiotherapy, allowing rapid production of biological building blocks that support cellular proliferation, and shielding against damaging mitochondrial free radicals. In this article, we highlight the interconnected roles of dysregulated pH dynamics in cancer initiation, progression, adaptation, and in determining the programming and re-programming of tumor cell metabolism.
The change of a normal, healthy cell to a transformed cell is the first step in the evolutionary arc of a cancer. While the role of oncogenes in this ‘passage’ is well known, the role of ion ...transporters in this critical step is less known and is fundamental to our understanding the early physiological processes of carcinogenesis. Cancer cells and tissues have an aberrant regulation of hydrogen ion dynamics leading to a reversal of the normal tissue intracellular to extracellular pH gradient (ΔpHi to ΔpHe). When this perturbation in pH dynamics occurs during carcinogenesis is less clear. Very early studies using the introduction of different oncogene proteins into cells observed a concordance between neoplastic transformation and a cytoplasmic alkalinization occurring concomitantly with a shift towards glycolysis in the presence of oxygen, i.e. ‘Warburg metabolism’. These processes may instigate a vicious cycle that drives later progression towards fully developed cancer where the reversed pH gradient becomes ever more pronounced. This review presents our understanding of the role of pH and the NHE1 in driving transformation, in determining the first appearance of the cancer ‘hallmark’ characteristics and how the use of pharmacological approaches targeting pH/NHE1 may open up new avenues for efficient treatments even during the first steps of cancer development.
The brown seaweed Ectocarpus siliculosus is an emerging model species distributed worldwide in temperate coastal ecosystems. Over 1500 strains of E. siliculosus are available in culture from a broad ...range of geographic locations and ecological niches. To elucidate the molecular mechanisms underlying its capacity to cope with different environmental and biotic stressors, genomic and transcriptomic studies are necessary; this requires the co-isolation of genomic DNA and total RNA. In brown algae, extraction of nucleic acids is hindered by high concentrations of secondary metabolites that co-precipitate with nucleic acids. Here, we propose a reliable, rapid and cost-effective procedure for the co-isolation of high-quality nucleic acids using small quantities of biomass (25-, 50- and 100 mg) from strains of E. siliculosus (RHO12; LIA4A; EC524 and REP10-11) isolated from sites with different environmental conditions. The procedure employs a high pH extraction buffer (pH 9.5) which contains 100 mM Tris-HCl and 150 mM NaCl, with the addition of 5 mM DTT and 1% sarkosyl to ensure maximum solubility of nucleic acids, effective inhibition of nuclease activity and removal of interfering contaminants (e.g. polysaccharides, polyphenols). The use of sodium acetate together with isopropanol shortened precipitation time and enhanced the yields of DNA/RNA. A phenol:chlorophorm:isoamyl alcohol step was subsequently used to purify the nucleic acids. The present protocol produces high yields of nucleic acids from only 25 mg of fresh algal biomass (0.195 and 0.284 µg mg(-1) fresh weigh of RNA and DNA, respectively) and the high quality of the extracted nucleic acids was confirmed through spectrophotometric and electrophoretic analyses. The isolated RNA can be used directly in downstream applications such as RT-PCR and the genomic DNA was suitable for PCR, producing reliable restriction enzyme digestion patterns. Co-isolation of DNA/RNA from different strains indicates that this method is likely to have wider applications for intra- and inter-specific studies on other brown algae.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Transient lysosomal damage after infection with cytosolic pathogens or silica crystals uptake results in protease leakage. Whether limited leakage of lysosomal contents into the cytosol affects the ...function of cytoplasmic organelles is unknown. Here, we show that sterile and non-sterile lysosomal damage triggers a cell death independent proteolytic remodelling of the mitochondrial proteome in macrophages. Mitochondrial metabolic reprogramming required leakage of lysosomal cathepsins and was independent of mitophagy, mitoproteases and proteasome degradation. In an in vivo mouse model of endomembrane damage, live lung macrophages that internalised crystals displayed impaired mitochondrial function. Single-cell RNA-sequencing revealed that lysosomal damage skewed metabolic and immune responses in alveolar macrophages subsets with increased lysosomal content. Functionally, drug modulation of macrophage metabolism impacted host responses to Mycobacterium tuberculosis infection in an endomembrane damage dependent way. This work uncovers an inter-organelle communication pathway, providing a general mechanism by which macrophages undergo mitochondrial metabolic reprograming after endomembrane damage.
An important prerequisite for successful multisensor integration is that the data from the reporting sensors are transformed to a common reference frame free of systematic or registration bias ...errors. If not properly corrected, the registration errors can seriously degrade the global surveillance system performance by increasing tracking errors and even introducing ghost tracks. The relative sensor registration (or grid-locking) process aligns remote data to local data under the assumption that the local data are bias free and that all biases reside with the remote sensor. In this paper, we consider all registration errors involved in the grid-locking problem, i.e., attitude, measurement, and position biases. A linear least squares (LS) estimator of these bias terms is derived and its statistical performance compared to the hybrid Cramér-Rao lower bound (HCRLB) as a function of sensor locations, sensors number, and accuracy of sensor measurements.
In the context of target tracking, the Posterior Cramér–Rao Lower Bound (PCRLB) provides a powerful tool to assess the optimal achievable accuracy of target state estimation. In the bistatic ...configuration both geometry factors and transmitted waveform play an important role in the estimation accuracy. In this paper, we derive the PCRLB on sequential target state estimation accuracy in a bistatic radar tracking scenario, in the most general case of uncertain target measurements, i.e. when the probability of detection is less than one and the probability of false alarm is greater than zero. Then, we propose a PCRLB-based algorithm for selecting the best transmitter of opportunity for the tracking of a radar target in a multisensor Passive Coherent Location (PCL) system.
•The PCRLB assesses the optimal achievable accuracy of target state estimation.•We calculate the PCRLB for uncertain target measurements in a bistatic radar.•We propose a PCRLB-based algorithm for channel selection in a multistatic radar.•We test the algorithm on a PCL system composed of a UMTS station and an FM station.
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