The mPEG-PCL Copolymer for Selective Fermentation of Staphylococcus lugdunensis Against Candida parapsilosis in the Human Microbiome.

Many human skin diseases, such as seborrheic dermatitis, potentially occur due to the over-growth of fungi. It remains a challenge to develop fungicides with a lower risk of generating resistant fungi and non-specifically killing commensal microbes. Our probiotic approaches using a selective fermentation initiator of skin commensal bacteria, fermentation metabolites or their derivatives provide novel therapeutics to rein in the over-growth of fungi. Staphylococcus lugdunensis (S. lugdunensis) bacteria and Candida parapsilosis (C. parapsilosis) fungi coexist in the scalp microbiome. S. lugdunensis interfered with the growth of C. parapsilosis via fermentation. A methoxy poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) copolymer functioned as a selective fermentation initiator of S. lugdunensis, selectively triggering the S. lugdunensis fermentation to produce acetic and isovaleric acids. The acetic acid and its pro-drug diethyleneglycol diacetate (Ac-DEG-Ac) effectively suppressed the growth of C. parapsilosis in vitro and impeded the fungal expansion in the human dandruff. We demonstrate for the first time that S. lugdunensis is a skin probiotic bacterium that can exploit mPEG-PCL to yield fungicidal short-chain fatty acids (SCFAs). The concept of bacterial fermentation as a part of skin immunity to re-balance the dysbiotic microbiome warrants a novel avenue for studying the probiotic function of the skin microbiome in promoting health

STI571 reduces TRAIL-induced apoptosis in colon cancer cells: c-Abl activation by the death receptor leads to stress kinase-dependent cell death

<p>Abstract</p> <p>Background</p> <p>In an effort to achieve better cancer therapies, we elucidated the combination cancer therapy of STI571 (an inhibitor of Bcr-Abl and clinically used for chronic myelogenous leukemia) and TNF-related apoptosis-inducing ligand (TRAIL, a developing antitumor agent) in leukemia, colon, and prostate cancer cells.</p> <p>Methods</p> <p>Colon cancer (HCT116, SW480), prostate cancer (PC3, LNCaP) and leukemia (K562) cells were treated with STI571 and TRAIL. Cell viability was determined by MTT assay and sub-G1 appearance. Protein expression and kinase phosphorylation were determined by Western blotting. c-Abl and p73 activities were inhibited by target-specific small interfering (si)RNA. In vitro kinase assay of c-Abl was conducted using CRK as a substrate.</p> <p>Results</p> <p>We found that STI571 exerts opposite effects on the antitumor activity of TRAIL. It enhanced cytotoxicity in TRAIL-treated K562 leukemia cells and reduced TRAIL-induced apoptosis in HCT116 and SW480 colon cancer cells, while having no effect on PC3 and LNCaP cells. In colon and prostate cancer cells, TRAIL caused c-Abl cleavage to the active form via a caspase pathway. Interestingly, JNK and p38 MAPK inhibitors effectively blocked TRAIL-induced toxicity in the colon, but not in prostate cancer cells. Next, we found that STI571 could attenuate TRAIL-induced c-Abl, JNK and p38 activation in HCT116 cells. In addition, siRNA targeting knockdown of c-Abl and p73 also reduced TRAIL-induced cytotoxicity, rendering HCT116 cells less responsive to stress kinase activation, and masking the cytoprotective effect of STI571.</p> <p>Conclusions</p> <p>All together we demonstrate a novel mediator role of p73 in activating the stress kinases p38 and JNK in the classical apoptotic pathway of TRAIL. TRAIL via caspase-dependent action can sequentially activate c-Abl, p73, and stress kinases, which contribute to apoptosis in colon cancer cells. Through the inhibition of c-Abl-mediated apoptotic p73 signaling, STI571 reduces the antitumor activity of TRAIL in colon cancer cells. Our results raise additional concerns when developing combination cancer therapy with TRAIL and STI571 in the future.</p

Transcription of the rat testis-specific Rtdpoz-T1 and -T2 retrogenes during embryo development: co-transcription and frequent exonisation of transposable element sequences

<p>Abstract</p> <p>Background</p> <p>Retrotransposition is an important evolutionary force for the creation of new and potentially functional intronless genes which are collectively called retrogenes. Many retrogenes are expressed in the testis and the gene products have been shown to actively participate in spermatogenesis and other unique functions of the male germline. We have previously reported a cluster of retrogenes in the rat genome that encode putative TRAF- and POZ-domain proteins. Two of the genes, <it>Rtdpoz-T1 and -T2 </it>(abbreviated as <it>T1 </it>and <it>T2</it>), have further been shown to be expressed specifically in the rat testis.</p> <p>Results</p> <p>We show here that the <it>T1 </it>and <it>T2 </it>genes are also expressed in the rat embryo up to days 16–17 of development when the genes are silenced until being re-activated in the adult testis. On database interrogation, we find that some <it>T1/T2 </it>exons are chromosomally duplicated as cassettes of 2 or 3 exons consistent with retro-duplication. The embryonic <it>T1/T2 </it>transcripts, characterised by RT-PCR-cloning and rapid amplification of cDNA ends, are further found to have acquired one or more noncoding exons in the 5'-untranslated region (5'-UTR). Most importantly, the <it>T1</it>/<it>T2 </it>locus is embedded within a dense field of relics of transposable element (TE) derived mainly from LINE1 and ERV sequences, and the TE sequences are frequently exonised through alternative splicing to form the 5'-UTR sequences of the <it>T1/T2 </it>transcripts. In a case of <it>T1 </it>transcript, the 3'-end is extended into and terminated within an L1 sequence. Since the two genes share a common exon 1 and are, therefore, regulated by a single promoter, a <it>T2</it>-to-<it>T1 </it>co-transcription model is proposed. We further demonstrate that the exonised 5'-UTR TE sequences could lead to the creation of upstream open reading frames resulting in translational repression.</p> <p>Conclusion</p> <p>Exonisation of TE sequences is a frequent event in the transcription of retrogenes during embryonic development and in the testis and may contribute to post-transcriptional regulation of expression of retrogenes.</p

Preparation and characterization of carboxyl-group functionalized superparamagnetic nanoparticles and t he potential for bio-applications

In this work, a method was developed to prepare monodispersed carboxyl-group functionalized magnetic nanoparticles. Nanosized maghemite (y-Fe2O3, 7.0 ± 1.0 nm) was synthesized using thermal co-precipitation method and subsequently coated with functional groups by one-step suspension copolymerization. The Fourier transform infrared spectroscopy study and thermogravitmetric analyses confirmed the successful functionalization of carboxyl groups on the surface of magnetic nanocrystals. The surface chemistry makes it possible for SPRI (solid phase reversible immobilization)-based DNA purification. Thus the nanoparticles were employed to isolate plasmid DNA from bacterial cell culture and the results demonstrated its applicability in DNA preparation

Immunotherapy for Glioblastomas

Glioblastoma (GBM), a WHO grade IV brain tumor, is an aggressive tumor with poor prognosis; even with current standard care of triple therapy, consisting of surgical resection, chemo and radiation therapy, the patients’ median survival time is only approximately 15 months. Recent practice shows that immunotherapy made some progress in some other solid tumors, like melanoma or non-small cell lung cancer. This chapter is going to review some advances in immunotherapy for GBM

Modeling and Validation of a Data Process Unit Control for Space Applications

International audienceData process unit (DPU) is a typical embedded system. It is widely used in space applications to collect data from sensors, process data and send the data to its upper master computer. In this paper, we use the BIP framework to model and validate a DPU system of a real space application. We first build the system model including the control software, hardware and the environment. Validation is by extensive simulation of a monitored system obtained as the composition of the DPU model with monitors. A monitor checks a requirement by continuously sensing the state of the model and reaching an error state if the requirement is violated. We checked fault-tolerance for di erent fault models and detected several errors that under some conditions, could correspond to real implementation errors

R\'{e}nyi Divergence Deep Mutual Learning

This paper revisits Deep Mutual Learning (DML), a simple yet effective computing paradigm. We propose using R\'{e}nyi divergence instead of the KL divergence, which is more flexible and tunable, to improve vanilla DML. This modification is able to consistently improve performance over vanilla DML with limited additional complexity. The convergence properties of the proposed paradigm are analyzed theoretically, and Stochastic Gradient Descent with a constant learning rate is shown to converge with $\mathcal{O}(1)$-bias in the worst case scenario for nonconvex optimization tasks. That is, learning will reach nearby local optima but continue searching within a bounded scope, which may help mitigate overfitting. Finally, our extensive empirical results demonstrate the advantage of combining DML and R\'{e}nyi divergence, which further improves generalized models