Notes

Inhibitory interneurons together with differential plasticities inside their contacts track excitatory/inhibitory balance within the spinal nociceptive technique.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.Bispecific antibodies come in many different formats, including the particularly interesting two-in-one antibodies, where one conventional IgG binds two different antigens. The IgG format allows these antibodies to mediate Fc-related functionality, and their wild-type structure ensures low immunogenicity and enables standard methods to be used for development. It is however difficult, time-consuming and costly to generate two-in-one antibodies. Herein we demonstrate a new approach to create a similar type of antibody by combining two different variable heavy (VH) domains in each Fab arm of an IgG, a tetra-VH IgG format. The VHs are used as building blocks, where one VH is placed at its usual position, and the second VH replaces the variable light (VL) domain in a conventional IgG. VH domains, binding several different types of antigens, were discovered and could be rearranged in any combination, offering a convenient "plug and play" format. The tetra-VH IgGs were found to be functionally tetravalent, binding two antigens on each arm of the IgG molecule simultaneously. This offers a new strategy to also create monospecific, tetravalent IgGs that, depending on antigen architecture and mode-of-action, may have enhanced efficacy compared to traditional bivalent antibodies.The biological function of non-thermal atmospheric pressure plasma has been widely accepted in several types of cancer. We previously developed plasma-activated medium (PAM) for clinical use, and demonstrated that PAM exhibits a metastasis-inhibitory effect on ovarian cancer through reduced MMP-9 secretion. However, the anti-tumor effects of PAM on endometrial cancer remain unknown. In this study, we investigated the inhibitory effect of PAM on endometrial cancer cell viability in vitro. Our results demonstrated that AMEC and HEC50 cell viabilities were reduced by PAM at a certain PAM ratio, and PAM treatment effectively increased autophagic cell death in a concentration dependent manner. In addition, we evaluated the molecular mechanism of PAM activity and found that the mTOR pathway was inactivated by PAM. Moreover, our results demonstrated that the autophagy inhibitor MHY1485 partially inhibited the autophagic cell death induced by PAM treatment. These findings indicate that PAM decreases the viability of endometrial cancer cells along with alteration of the mTOR pathway, which is critical for cancer cell viability. Collectively, our data suggest that PAM inhibits cell viability while inducing autophagic cell death in endometrial cancer cells, representing a potential novel treatment for endometrial cancer.An amendment to this paper has been published and can be accessed via a link at the top of the paper.Central nervous system infection (CNSI) is a significant type of infection that plagues the fields of neurology and neurosurgical science. Crenolanib Prompt and accurate diagnosis of CNSI is a major challenge in clinical and laboratory assessments; however, developing new methods may help improve diagnostic protocols. This study evaluated the second-generation micro/nanofluidic chip platform (MNCP-II), which overcomes the difficulties of diagnosing bacterial and fungal infections in the CNS. The MNCP-II is simple to operate, and can identify 44 genus or species targets and 35 genetic resistance determinants in 50 minutes. To evaluate the diagnostic accuracy of the second-generation micro/nanofluidic chip platform for CNSI in a multicenter study. The limit of detection (LOD) using the second-generation micro/nanofluidic chip platform was first determined using six different microbial standards. A total of 180 bacterium/fungi-containing cerebrospinal fluid (CSF) cultures and 26 CSF samples collected from CNSI patients witis a very effective molecular detection platform that can assist in the diagnosis of CNSI and can significantly improve diagnostic efficiency.Erectile dysfunction (ED) is a common disorder among men, with significant public health implications. Current therapies have certain limitations including efficacy and safety issues, necessitating the development of novel therapeutic strategies for ED. Nanotechnology-based drug delivery systems are being explored to overcome these limitations with promising in vitro and in vivo efficacies. In particular, lipid-based nanoparticles have generated considerable interest owing to their potential to enhance drug bioavailability, and decrease side effects and drug susceptibility to metabolism. This review summarizes the recent findings using lipid-based nanoparticles in ED therapy.COMP-4, a nutraceutical combination consisting of ginger rhizome, muira puama, Paullinia cupana, and L-citrulline, enhances intracellular nitric oxide (NO) production by the corporal smooth muscle cells (CSMC). This study aims to determine if the previously shown beneficial effect of COMP-4 on the histology and function of the aging penis is associated with an antioxidative effect from endogenously produced NO. Ten-month-old male rats were treated daily for 2 months with COMP-4 or vehicle at which time the corpora and penile dorsal artery (PDA) were evaluated by immunohistochemistry for (a) apoptosis (b) proliferative cell nuclear antigen, (c) heme oxygenase-1 (HO-1), (d) myeloperoxidase (MPO), and (e) nitrotyrosine (NT). CSMC were cultured and incubated with COMP-4 in order to determine intracellular oxidative stress via the GSH/GSSG ratio. In both the corpora and PDA, daily treatment with COMP-4 resulted in an increase in both smooth muscle cell proliferation and HO-1 expression as well as a decrease in MPO. There was no change in either apoptosis or NT expression. In the CSMC cell culture, treatment with COMP-4 increased the intracellular GSH/GSSG ratio. COMP-4 appears to have an antioxidant effect on the aging vascular smooth muscle cells both in the corpora and peripheral vasculature.An amendment to this paper has been published and can be accessed via a link at the top of the paper.The ability to image pressure distribution over complex three-dimensional surfaces would significantly augment the potential applications of electronic skin. However, existing methods show poor spatial and temporal fidelity due to their limited pixel density, low sensitivity, or low conformability. Here, we report an ultraflexible and transparent electroluminescent skin that autonomously displays super-resolution images of pressure distribution in real time. The device comprises a transparent pressure-sensing film with a solution-processable cellulose/nanowire nanohybrid network featuring ultrahigh sensor sensitivity (>5000 kPa-1) and a fast response time (1000 dpi) pressure imaging without the need for pixel structures. link2 Our approach provides a new framework for visualizing accurate stimulus distribution with potential applications in skin prosthesis, robotics, and advanced human-machine interfaces.Early maturing varieties of soybean have a high yield potential in Europe, where the main biotic threat to soybean cultivation are root lesion nematodes (Pratylenchus spp.). Nitrogen fixation in root nodules by highly efficient inoculants of Bradyrhizobium japonicum is an incentive to grow soybean in low-input rotation systems. We investigated density-dependent effects of Pratylenchus penetrans on nitrogen fixation by co-inoculated B. japonicum. Less than 130 inoculated nematodes affected the number and weight of nodules, the density of viable bacteroids in nodules, and nitrogen fixation measured as concentration of ureides in leaves. With more inoculated nematodes, the percentage that invaded the roots increased, and adverse effects on the symbiosis accelerated, leading to non-functional nodules at 4,000 and more nematodes. When P. penetrans invaded roots that had fully established nodules, growth of nodules, density of bacteroids, and nitrogen fixation were affected but not the number of nodules. In contrast, nodulation of already infested roots resulted in a high number of small nodules with decreased densities of bacteroids and nitrogen fixation. P. penetrans invaded and damaged the nodules locally, but they also significantly affected the nodule symbiosis by a plant-mediated mechanism, as shown in an experiment with split-root systems.It is still not understood how honey bee parasite changes the gene expression to adapt to the host environment and how the host simultaneously responds to the parasite infection by modifying its own gene expression. To address this question, we studied a trypanosomatid, Lotmaria passim, which can be cultured in medium and inhabit the honey bee hindgut. We found that L. passim decreases mRNAs associated with protein translation, glycolysis, detoxification of radical oxygen species, and kinetoplast respiratory chain to adapt to the anaerobic and nutritionally poor honey bee hindgut during the infection. link3 After the long term infection, the host appears to be in poor nutritional status, indicated by the increase and decrease of take-out and vitellogenin mRNAs, respectively. Simultaneous gene expression profiling of L. passim and honey bee during infection by dual RNA-seq provided insight into how both parasite and host modify their gene expressions.Which factors are related to false negative results of the interferon-γ release assay (IGRA) is unclear. This systematic review described the risk factors associated with false negative IGRA results. Two authors independently identified studies designed to evaluate risk factors for false negative IGRA results from PubMed, the Cochrane Register of Control Trial database, and EMBASE, accessed on October 22, 2018. Meta-analyses were conducted with random-effect models, and heterogeneity was calculated with the I2 method. Of 1,377 titles and abstracts screened, 47 full texts were selected for review, and we finally included 17 studies in this systematic review. The most commonly studied risk factor (14 studies) was advanced age, followed by low peripheral lymphocyte counts (7 studies), and these factors were associated with false negative results even with different tuberculosis incidences (pooled odds ratio 2.06; 95% CI, 1.68-2.52 in advanced age and 2.68; 95% CI, 2.00-3.61 in low peripheral lymphocyte counts). Advanced age and low peripheral lymphocyte counts may be common risk factors for false negative IGRA results, suggesting that people with these factors need to be carefully followed, even if they have negative IGRA results.Characterizing upper airway occlusion during natural sleep could be instrumental for studying the dynamics of sleep apnea and designing an individualized treatment plan. In recent years, obstructive sleep apnea (OSA) phenotyping has gained attention to classify OSA patients into relevant therapeutic categories. Electrical impedance tomography (EIT) has been lately suggested as a technique for noninvasive continuous monitoring of the upper airway during natural sleep. In this paper, we developed the automatic data processing and feature extract methods to handle acquired EIT data for several hours. Removing ventilation and blood flow artifacts, EIT images were reconstructed to visualize how the upper airway collapsed and reopened during the respiratory event. From the time series of reconstructed EIT images, we extracted the upper airway closure signal providing quantitative information about how much the upper airway was closed during collapse and reopening. Features of the upper airway dynamics were defined from the extracted upper airway closure signal and statistical analyses of ten OSA patients' data were conducted.
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