Ongoing clinical studies on patients recently implanted with the auditory midbrain implant (AMI) into the inferior colliculus (IC) for hearing restoration have shown that these patients do not achieve performance levels comparable to cochlear implant patients. The AMI consists of a single-shank array (20 electrodes) for stimulation along the tonotopic axis of the IC. Recent findings suggest that one major limitation in AMI performance is the inability to sufficiently activate neurons across the three-dimensional (3-D) IC. Unfortunately, there are no currently available 3-D array technologies that can be used for clinical applications. More recently, there has been a new initiative by the European Commission to fund and develop 3-D chronic electrode arrays for science and clinical applications through the NeuroProbes project that can overcome the bulkiness and limited 3-D configurations of currently available array technologies. As part of the NeuroProbes initiative, we investigated whether their new array technology could be potentially used for future AMI patients. Since the NeuroProbes technology had not yet been tested for electrical stimulation in an in vivo animal preparation, we performed experiments in ketamine-anesthetized guinea pigs in which we inserted and stimulated a NeuroProbes array within the IC and recorded the corresponding neural activation within the auditory cortex. We used 2-D arrays for this initial feasibility study since they were already available and were sufficient to access the IC and also demonstrate effective activation of the central auditory system. Based on these encouraging results and the ability to develop customized 3-D arrays with the NeuroProbes technology, we can further investigate different stimulation patterns across the ICC to improve AMI performance. 相似文献
A hot new topic in medical treatment is the use of mesenchymal stem cells (MSC) in therapy. The low frequency of this subpopulation
of stem cells in bone marrow (BM) necessitates their in vitro expansion prior to clinical use. We evaluated the effect of
long term culture on the senescence of these cells. 相似文献
Excessive amounts of heavy metals adversely affect plant growth and development. Whereas some regions naturally contain high
levels of heavy metals, anthropogenic release of heavy metals into the environment continuously increases soil contamination.
Preliminary studies have shown that Chenopodium botrys can grow in some heavy metal contaminated soils and is a high accumulator plant species for Cu and moderately accumulator
plant species for Fe, Mn, and Zn, thus, was considered as an important species in this study. Based on that, in this species,
we studied the individual effects of heavy metals on the formation, development, and structure of anther and pollen. To achieve
this purpose, surrounding area of Hame-Kasi iron and copper mine (Hamedan, Iran) was chosen as a polluted area where the amount
of some heavy metals was several times higher than the natural soils. Flowers and young pods were removed from non-polluted
and polluted plants, fixed in FAA 70, and subjected to developmental studies. Analysis of anther development in plants from
contaminated sites showed general similarities in the pattern of pollen formation with those from non-polluted ones, but also
deviation from typical form of major stages of anther and pollen development was seen in plants from polluted ones. Stabilizing
of tapetum layer, increasing in tapetum layer numbers, thickening callose wall in the microspore mother cell stage, changing
the anther shape, and decreasing the size of anther were the effects of heavy metals. Reduction of pollen number was also
seen in the plants collected from polluted area. 相似文献
Methylmercury (MeHg) is the most toxic form of mercury which is bioaccumulated in the aquatic food chain. It has been shown that one of the main targets of MeHg toxicity is the brain, but there is little knowledge of the molecular mechanisms of its toxic effects. In this work we used a proteomics analysis to determine the changes in the brain proteome of juvenile beluga (Huso huso) exposed to dietary MeHg. The juvenile beluga were fed the diet containing 0.8 ppm MeHg for 70 days. Proteins of the brain tissue were analyzed using two-dimensional electrophoresis and MALDI-TOF/TOF mass spectrometry. We found eight proteins with significant altered expression level in the fish brain exposed to MeHg. These proteins are involved in different cell functions including cell metabolism, protein folding, cell division, and signal transduction. Our results support the idea that MeHg exerts its toxicity through oxidative stress induction and apoptotic effects. They also suggest that chronic MeHg exposure would induce an important metabolic deficiency in the brain. These findings provide basic information to understand possible mechanisms of MeHg toxicity in aquatic ecosystems. 相似文献
Targeted delivery of therapeutic molecules into cancer cells is considered as a promising strategy to tackle cancer. Antibody–drug conjugates (ADCs), in which a monoclonal antibody (mAb) is conjugated to biologically active drugs through chemical linkers, have emerged as a promising class of anticancer treatment agents, being one of the fastest growing fields in cancer therapy. The failure of early ADCs led researchers to explore strategies to develop more effective and improved ADCs with lower levels of unconjugated mAbs and more-stable linkers between the drug and the antibody, which show improved pharmacokinetic properties, therapeutic indexes, and safety profiles. Such improvements resulted in the US Food and Drug Administration approvals of brentuximab vedotin, trastuzumab emtansine, and, more recently, inotuzumab ozogamicin. In addition, recent clinical outcomes have sparked additional interest, which leads to the dramatically increased number of ADCs in clinical development. The present review explores ADCs, their main characteristics, and new research developments, as well as discusses strategies for the selection of the most appropriate target antigens, mAbs, cytotoxic drugs, linkers, and conjugation chemistries. 相似文献
The epithelial cell adhesion molecule (EpCAM) is a Type I transmembrane superficial glycoprotein antigen that is expressed on the surface of basolateral membrane of multiple epithelial cells with some exceptions such as epidermal keratinocytes, hepatocytes, thymic cortical epithelial cells, squamous stratified epithelial cells, and myoepithelial cells that do not express the molecule. The molecule plays a pivotal role in the structural integrity, adhesion of the epithelial tissues and their interaction with the underlying layers. EpCAM prevents claudin-7 and claudin-1 molecules from degradation, thereby, decreasing the number of tight junctions and cellular interconnections, and promoting the cells toward carcinogenic transformation. Moreover, the mutations in the EpCAM gene lead to congenital tufting enteropathy, severe intestinal epithelium homeostasis disorders, and Lynch and Lynch syndrome. Overexpression of EpCAM on stem cells of some cancers and the presence of this molecule on circulating tumor cells (CTCs) makes it a promising candidate for cancer diagnosis as well as tracing and isolation of CTCs. 相似文献
Volatile organic compounds (VOCs) produced by bacteria have significant potential to control phytopathogens. In this study, the VOCs produced by endofungal bacteria Pseudomonas sp. Bi1, Bacillus sp. De3, Pantoea sp. Ma3 and Pseudomonas sp. De1 isolated from wild growing mushrooms were evaluated in vitro for their antagonistic activity against Pseudomonas tolaasii Pt18, the causal agent of mushroom brown blotch disease. The gas chromatography–mass spectrometry (GC–MS) analysis revealed that strains Pseudomonas sp. Bi1, Pseudomonas sp. De1, Bacillus sp. De3 and Pantoea sp. Ma3 produced eight, sixteen, nine, and twelve VOCs, respectively. All antagonistic endofungal bacteria produced VOCs which significantly reduced brown blotch symptoms on mushroom caps and inhibited the growth of P. tolaasii Pt18 at the varying levels. Scanning electron microscopy revealed severe morphological changes in cells of P. tolaasii Pt18 following exposure to the VOCs of Pseudomonas sp. Bi1 and De1. Furthermore, The VOCs produced by endofungal bacteria significantly reduced swarming, swimming, twitching, chemotaxis motility and biofilm formation by P. tolaasii Pt18 cells, which are essential contributors to pathogenicity. This is to first report about the inhibition effects of VOCs produced by antagonistic bacteria on virulence traits of P. tolaasii. Our findings provide new insights regarding the potential of antibacterial VOCs as a safe fumigant to control mushroom brown blotch disease.
International Journal of Peptide Research and Therapeutics - Appetite is controlled by a complex system of central and peripheral signals interacting to modulate the ingestion response. Several... 相似文献