The chlamydial periplasmic stress response serine protease cHtrA is secreted into host cell cytosol

<p>Abstract</p> <p>Background</p> <p>The periplasmic High Temperature Requirement protein A (HtrA) plays important roles in bacterial protein folding and stress responses. However, the role of chlamydial HtrA (cHtrA) in chlamydial pathogenesis is not clear.</p> <p>Results</p> <p>The cHtrA was detected both inside and outside the chlamydial inclusions. The detection was specific since both polyclonal and monoclonal anti-cHtrA antibodies revealed similar intracellular labeling patterns that were only removed by absorption with cHtrA but not control fusion proteins. In a Western blot assay, the anti-cHtrA antibodies detected the endogenous cHtrA in Chlamydia-infected cells without cross-reacting with any other chlamydial or host cell antigens. Fractionation of the infected cells revealed cHtrA in the host cell cytosol fraction. The periplasmic cHtrA protein appeared to be actively secreted into host cell cytosol since no other chlamydial periplasmic proteins were detected in the host cell cytoplasm. Most chlamydial species secreted cHtrA into host cell cytosol and the secretion was not inhibitable by a type III secretion inhibitor.</p> <p>Conclusion</p> <p>Since it is hypothesized that chlamydial organisms possess a proteolysis strategy to manipulate host cell signaling pathways, secretion of the serine protease cHtrA into host cell cytosol suggests that the periplasmic cHtrA may also play an important role in chlamydial interactions with host cells.</p

A novel nanoparticle drug delivery system based on PEGylated hemoglobin for cancer therapy

Proteins such as albumin, gelatin, casein, transferrin, and collagen are widely used as drug delivery systems. However, only albumin-based paclitaxel (PTX) formulation AbraxaneVR (PTX-albumin NPs prepared by nab-technology) has been successfully developed for treating metastatic breast cancer clinically due to abundant materials, simple industrial scale-up process, and well tumor-targeting ability. Hemoglobin (Hb) is another protein used for drug delivery with similar advantages. In this study, we successfully synthesized PEG-Hb nanoparticles loading with PTX based on previously well-established acid-denatured method. PEG-Hb-PTX NPs showed enhanced cellular uptake and great cellular inhibition ability in vitro. Moreover, our animal study showed that PEGylated NPs greatly accumulated in tumor tissues and exhibited excellent anticancer activity in vivo. We found that PEG-Hb-PTX NPs possess a better in vivo antitumor effect than the commercially available TaxolVR formulation. We believe that PEG-Hb has great potential as an efficient drug delivery system for further clinic study

A hybrid motion planning framework for autonomous driving in mixed traffic flow

As a core part of an autonomous driving system, motion planning plays an important role in safe driving. However, traditional model- and rule-based methods lack the ability to learn interactively with the environment, and learning-based methods still have problems in terms of reliability. To overcome these problems, a hybrid motion planning framework (HMPF) is proposed to improve the performance of motion planning, which is composed of learning-based behavior planning and optimization-based trajectory planning. The behavior planning module adopts a deep reinforcement learning (DRL) algorithm, which can learn from the interaction between the ego vehicle (EV) and other human-driven vehicles (HDVs), and generate behavior decision commands based on environmental perception information. In particular, the intelligent driver model (IDM) calibrated based on real driving data is used to drive HDVs to imitate human driving behavior and interactive response, so as to simulate the bidirectional interaction between EV and HDVs. Meanwhile, trajectory planning module adopts the optimization method based on road Frenet coordinates, which can generate safe and comfortable desired trajectory while reducing the solution dimension of the problem. In addition, trajectory planning also exists as a safety hard constraint of behavior planning to ensure the feasibility of decision instruction. The experimental results demonstrate the effectiveness and feasibility of the proposed HMPF for autonomous driving motion planning in urban mixed traffic flow scenarios

Changes in the Expression of miR-381 and miR-495 Are Inversely Associated with the Expression of the MDR1 Gene and Development of Multi-Drug Resistance

Multidrug resistance (MDR) frequently develops in cancer patients exposed to chemotherapeutic agents and is usually brought about by over-expression of P-glycoprotein (P-gp) which acts as a drug efflux pump to reduce the intracellular concentration of the drug(s). Thus, inhibiting P-gp expression might assist in overcoming MDR in cancer chemotherapy. MiRNAome profiling using next-generation sequencing identified differentially expressed microRNAs (miRs) between parental K562 cells and MDR K562 cells (K562/ADM) induced by adriamycin treatment. Two miRs, miR-381 and miR-495, that were strongly down-regulated in K562/ADM cells, are validated to target the 3'-UTR of the MDR1 gene. These miRs are located within a miR cluster located at chromosome region 14q32.31, and all miRs in this cluster appear to be down-regulated in K562/ADM cells. Functional analysis indicated that restoring expression of miR-381 or miR-495 in K562/ADM cells was correlated with reduced expression of the MDR1 gene and its protein product, P-gp, and increased drug uptake by the cells. Thus, we have demonstrated that changing the levels of certain miR species modulates the MDR phenotype in leukemia cells, and propose further exploration of the use of miR-based therapies to overcome MDR.The authors would like to declare that we received funding from a commercial source, i.e. Bioplatforms Australia. This does not alter the authors' adherence to all PLOS ONE policies on sharing data and materials

1.28 and 5.12 Gbps multi-channel twinax cable receiver ASICs for the ATLAS Inner Tracker Pixel Detector Upgrade

We present two prototypes of a gigabit transceiver ASIC, GBCR1 and GBCR2, both designed in a 65-nm CMOS technology for the ATLAS Inner Tracker Pixel Detector readout upgrade. The first prototype, GBCR1, has four upstream receiver channels and one downstream transmitter channel with pre-emphasis. Each upstream channel receives the data at 5.12 Gbps through a 5 meter AWG34 Twinax cable from an ASIC driver located on the pixel module and restores the signal from the high frequency loss due to the low mass cable. The signal is retimed by a recovered clock before it is sent to the optical transmitter VTRx+. The downstream driver is designed to transmit the 2.56 Gbps signal from lpGBT to the electronics on the pixel module over the same cable. The peak-peak jitter (throughout the paper jitter is always peak-peak unless specified) of the restored signal is 35.4 ps at the output of GBCR1, and 138 ps for the downstream channel at the cable ends. GBCR1 consumes 318 mW and is tested. The second prototype, GBCR2, has seven upstream channels and two downstream channels. Each upstream channel works at 1.28 Gbps to recover the data directly from the RD53B ASIC through a 1 meter custom FLEX cable followed by a 6 meter AWG34 Twinax cable. The equalized signal of each upstream channel is retimed by an input 1.28 GHz phase programmable clock. Compared with the signal at the FLEX input, the additional jitter of the equalized signal is about 80 ps when the retiming logic is o . When the retiming logic is on, the jitter is 50 ps at GBCR2 output, assuming the 1.28 GHz retiming clock is from lpGBT. The downstream is designed to transmit the 160 Mbps signal from lpGBT through the same cable connection to RD53B and the jitter is about 157 ps at the cable ends. GBCR2 consumes about 150 mW when the retiming logic is on. This design was submitted in November 2019.Comment: 7 pages, 15 figure