Possible role of TGF-B pathways in schizophrenia

© 2016, University of Kragujevac, Faculty of Science. All Rights Reserved. The phenomenological uniqueness of each patient with schizophrenia is determined by complex symptomatology, particularly the overlapping of symptoms and their prominence in certain phases of this mental disorder. Establishing biological markers is an important step in the further objectivisation and quantification of schizophrenia. Identifying the cytokine profiles that precede a psychotic episode could direct the strategies for relapse prevention and be useful in predicting disease progression and treatment response. In the context of inflammation, TGF-β exerts potent anti-inflammatory and immunosuppressive functions by inhibiting pro-inflammatory cytokine synthesis, but it can also have pro-inflammatory functions through its stimulatory effects on inflammatory 17 cells. It has been shown that the T helper cell type-1 and type-17 responses are reduced and type-2 response is increased in patients with schizophrenia. Both data from the literature and our results also indicate the presence of an anti-inflammatory response through production of the TGF-β regulatory cytokine. A meta-analysis of plasma cytokine alterations suggested that TGF-β is the state marker for acute exacerbation of schizophrenia, and we showed that TGF-β can also be a valuable marker for psychosis. Hyperactivity of TGF-β signalling pathways in schizophrenia may be both a neuroprotective mechanism and a possible therapeutic target

IL-33/ST2 axis in innate and acquired immunity to tumors

Interleukin-33, a ligand for ST2/T1, has an important role in allergy, autoimmunity and inflammation. The role of IL-33/ST2 axis in cancer is not elucidated. Using metastatic breast cancer model we provide evidence that lack of ST2 signaling led to reduced tumor growth and metastasis and enhanced anti-tumor immunity

Trend of suicide by self-immolation in a 13-year timeline: was the COVID-19 pandemic a potentially important stressor?

IntroductionSelf-immolation is an uncommon way of attempting and committing a suicide, with a fatality rate of 80%. The risk factors in self-immolation victims vary depending on demographic characteristics, socio-economic and cultural factors as well as religious beliefs. Whether the COVID-19 pandemic was a potentially important stressor for self-immolation is still unknown, with insufficient studies examining this issue. Therefore, in this study, we aimed to examine the trend of self-immolation in a 13-year timeline, and the potential association of COVID-19 pandemic with the increase in the incidence and severity of self-immolation injuries in Serbia in 2021.Materials and methodsThe study included hospitalized patients due to intentional burns caused by self-immolation in the period from January 1, 2008 to December 31, 2021. Joinpoint regression analysis was used for the analysis of continuous linear trends of self-immolation cases with change points.ResultsWhile a rising trend was observed in the 2008–2013 time segment, followed by a decline in the upcoming 2013–2016 time segment, a significant increase reached its maximum during COVID-19 pandemic (2021), with annual percent change of 37.1% (p = 0.001). A significant increase in the median number of cases per year was observed during 2021 compared to the previous periods (7.5 vs. 2). Frequency of patients with a psychiatric diagnosis vs. those without a psychiatric diagnosis was significantly higher during than before the COVID-19 period (66.7 vs. 36.1%, p = 0.046).ConclusionIn our study, a significant increase in the frequency of suicide attempts by self-immolation during COVID-19 pandemic was noticed. There was also an increased frequency of pre-existing psychiatric illness among patients during the pandemic period. With limited high-quality data available, the study adds to a rising body of evidence for assessment of outcomes of the pandemic on mental health and recognition of stressors for self-immolation

Global monitoring of antimicrobial resistance based on metagenomics analyses of urban sewage

Antimicrobial resistance (AMR) is a serious threat to global public health, but obtaining representative data on AMR for healthy human populations is difficult. Here, we use meta-genomic analysis of untreated sewage to characterize the bacterial resistome from 79 sites in 60 countries. We find systematic differences in abundance and diversity of AMR genes between Europe/North-America/Oceania and Africa/Asia/South-America. Antimicrobial use data and bacterial taxonomy only explains a minor part of the AMR variation that we observe. We find no evidence for cross-selection between antimicrobial classes, or for effect of air travel between sites. However, AMR gene abundance strongly correlates with socio-economic, health and environmental factors, which we use to predict AMR gene abundances in all countries in the world. Our findings suggest that global AMR gene diversity and abundance vary by region, and that improving sanitation and health could potentially limit the global burden of AMR. We propose metagenomic analysis of sewage as an ethically acceptable and economically feasible approach for continuous global surveillance and prediction of AMR.Peer reviewe

Setting a baseline for global urban virome surveillance in sewage

The rapid development of megacities, and their growing connectedness across the world is becoming a distinct driver for emerging disease outbreaks. Early detection of unusual disease emergence and spread should therefore include such cities as part of risk-based surveillance. A catch-all metagenomic sequencing approach of urban sewage could potentially provide an unbiased insight into the dynamics of viral pathogens circulating in a community irrespective of access to care, a potential which already has been proven for the surveillance of poliovirus. Here, we present a detailed characterization of sewage viromes from a snapshot of 81 high density urban areas across the globe, including in-depth assessment of potential biases, as a proof of concept for catch-all viral pathogen surveillance. We show the ability to detect a wide range of viruses and geographical and seasonal differences for specific viral groups. Our findings offer a cross-sectional baseline for further research in viral surveillance from urban sewage samples and place previous studies in a global perspective

Improving carbon nanotube nanodevices: Ambipolar field effect transistors and high -current interconnects

Early studies of electron transport in single-wall carbon nanotubes (SWNTs) have been hindered by large resistance of the nanotube-contact interface and weak electrostatic coupling to the gate electrode. Several groups have shown that the contact resistance can be reduced to kΩ range by growing nanotubes directly on the substrate using chemical vapor deposition (CVD). In our work we implement this growth technique by fabricating electrodes from cobalt, which creates perfectly transparent nanotube-electrode contacts, [special characters omitted] = 0.98. In addition, we use high temperature anneal in hydrogen atmosphere to reduce defect density in the dielectric layer and enhance gate effectiveness. At low temperatures we reduce the amount of gate voltage needed to add a single electron to 0.8 μm long nanotube by an order of magnitude to 15 mV. Using these improvements, we demonstrate ambipolar transport in nanotube-based field effect transistor (TubeFET), and use it to develop a novel type of memory device for data storage. In a metallic nanotube, we show that gate voltage can be used to tune the reflection probability of defect-induced scattering centers. Furthermore, total scattering probability increases with device length, suggesting weak scattering from molecular adsorbates. Studies of resistance in metallic nanotubes reveal both metallic and insulating temperature behaviors, depending on the total reflection probability in the device. Recently, it has been observed that metallic nanotubes can carry up to 25 μA of current at high bias. Our work indicates that the observed current saturation phenomena are not a contact-related issue, but rather due to electron-phonon scattering. Moreover, we demonstrate a tunable change in current carrying capacity, up to 40 μA, and functional form of the current-voltage (I − V) characteristic. These changes can be understood quantitatively within a model predicting a transition between stimulated and spontaneous phonon emission as a function of the nanotube Fermi energy. Finally, we present the first observation of current saturation in semiconducting nanotubes which are in qualitative agreement with the phonon emission model

Improving carbon nanotube nanodevices: Ambipolar field effect transistors and high -current interconnects

Early studies of electron transport in single-wall carbon nanotubes (SWNTs) have been hindered by large resistance of the nanotube-contact interface and weak electrostatic coupling to the gate electrode. Several groups have shown that the contact resistance can be reduced to kΩ range by growing nanotubes directly on the substrate using chemical vapor deposition (CVD). In our work we implement this growth technique by fabricating electrodes from cobalt, which creates perfectly transparent nanotube-electrode contacts, [special characters omitted] = 0.98. In addition, we use high temperature anneal in hydrogen atmosphere to reduce defect density in the dielectric layer and enhance gate effectiveness. At low temperatures we reduce the amount of gate voltage needed to add a single electron to 0.8 μm long nanotube by an order of magnitude to 15 mV. Using these improvements, we demonstrate ambipolar transport in nanotube-based field effect transistor (TubeFET), and use it to develop a novel type of memory device for data storage. In a metallic nanotube, we show that gate voltage can be used to tune the reflection probability of defect-induced scattering centers. Furthermore, total scattering probability increases with device length, suggesting weak scattering from molecular adsorbates. Studies of resistance in metallic nanotubes reveal both metallic and insulating temperature behaviors, depending on the total reflection probability in the device. Recently, it has been observed that metallic nanotubes can carry up to 25 μA of current at high bias. Our work indicates that the observed current saturation phenomena are not a contact-related issue, but rather due to electron-phonon scattering. Moreover, we demonstrate a tunable change in current carrying capacity, up to 40 μA, and functional form of the current-voltage (I − V) characteristic. These changes can be understood quantitatively within a model predicting a transition between stimulated and spontaneous phonon emission as a function of the nanotube Fermi energy. Finally, we present the first observation of current saturation in semiconducting nanotubes which are in qualitative agreement with the phonon emission model

The role of regulatory T cells in the modulation of anti-tumor immune response

Regulatory T cells (Treg) represent a subset of CD4+T{cyrillic} cells whose function is to suppress immune responses. Treg lymphocytes can be divided into two subsets: natural nTreg lymphocytes that are developed in the thymus and inducible iTreg lymphocytes, which originate from conventional T lymphocytes on the periphery. The majority of Treg lymphocytes express high levels of interleukin-2 (IL-2) receptor α chain (CD25) and transcription factor FoxP3 (critical for the development and suppressor activity of iTreg lymphocytes). Cancer cells can modulate anti-tumor immune response indirectly, through the activation of Treg lymphocytes. It has been shown that the loss of regulatory function by depletion of tumor-induced Treg lymphocytes may enhance effectors response, resulting in tumor rejection, while the increased number of Treg lymphocytes effectively prevents tumor destruction. nTreg lymphocytes express increasingly CTLA-4 and membranebound TGF-β, which inhibits cytokine production and responses of effectors lymphocytes. iTreg lymphocytes secrete immunosuppressive cytokines such as IL-10 and TGF-β. Treg lymphocytes represent one of important obstruction in anti-tumor immunity

The role of regulatory T cells in the modulation of anti-tumor immune response

Regulatory T cells (Treg) represent a subset of CD4+T{cyrillic} cells whose function is to suppress immune responses. Treg lymphocytes can be divided into two subsets: natural nTreg lymphocytes that are developed in the thymus and inducible iTreg lymphocytes, which originate from conventional T lymphocytes on the periphery. The majority of Treg lymphocytes express high levels of interleukin-2 (IL-2) receptor α chain (CD25) and transcription factor FoxP3 (critical for the development and suppressor activity of iTreg lymphocytes). Cancer cells can modulate anti-tumor immune response indirectly, through the activation of Treg lymphocytes. It has been shown that the loss of regulatory function by depletion of tumor-induced Treg lymphocytes may enhance effectors response, resulting in tumor rejection, while the increased number of Treg lymphocytes effectively prevents tumor destruction. nTreg lymphocytes express increasingly CTLA-4 and membranebound TGF-β, which inhibits cytokine production and responses of effectors lymphocytes. iTreg lymphocytes secrete immunosuppressive cytokines such as IL-10 and TGF-β. Treg lymphocytes represent one of important obstruction in anti-tumor immunity