Objective
To investigate oxidative stress markers and antioxidants in bipolar disorder (BD).
Methods
Electronic MEDLINE/PubMed/Cochrane‐Library/Scopus/TripDatabase search until 06/30/2019 for studies ...comparing antioxidant or oxidative stress markers between BD and healthy controls (HCs). Standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated for ≥3 studies.
Results
Forty‐four studies (n = 3,767: BD = 1,979; HCs = 1,788) reported on oxidative stress markers malondialdehyde (MDA), thiobarbituric acid reactive substances (TBARS), and total nitrites; antioxidants glutathione (GSH), uric acid, and zinc; or antioxidantenhancing enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and GSH‐transferase (GST). Compared with HCs, BD was associated with higher GST (P = .01), CAT (P = .02), nitrites (P < .0001), TBARS (P < .0001), MDA (P = .01), uric acid (P < .0001), and lower GSH (P = .006), without differences in SOD, GPX, and zinc. Compared to HCs, levels were higher in BD‐mania for TBARS (P < .0001) and uric acid (P < .0001); in BD‐depression for TBARS (P = .02); and BD‐euthymia for uric acid (P = .03). Uric acid levels were higher in BD‐mania vs BD‐depression (P = .002), but not vs BD euthymia. TBARS did not differ between BD‐mania and BD‐depression. Medication‐free BD‐mania patients had higher SOD (P = .02) and lower GPX (P < .0001) than HCs. After treatment, BD did not differ from HCs regarding SOD and GPX.
Conclusions
Beyond a single biomarker of oxidative stress, the combination of several parameters appears to be more informative for BD in general and taking into account illness polarity. BD is associated with an imbalance in oxidative stress with some phase‐specificity for uric acid and TBARS and possible treatment benefits for SOD and GPX. Future studies should take into account confounding factors that can modify oxidative stress status and simultaneously measure oxidative stress markers and antioxidants including different blood sources.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Soil organic C (SOC) is the largest terrestrial C pool, and it influences diverse soil properties and processes in a landscape. At global scales, SOC is related to climate; as climate changes, we ...expect that SOC will change at broad scales as well, but how SOC will respond to climate change in diverse environments is complex and highly uncertain. To evaluate the potential impact of predicted changes in temperature and precipitation across central Chile, we first estimated current SOC content using pedon descriptions and environmental variables (temperature, rainfall, land use, topography, soil types, and geology) as predictors. A random forest statistical model was used to predict SOC content by pedon data. Maps were created for six standard depths of the GlobalSoilMap project. Results showed mean SOC of 54 g kg−1 at a depth interval of 0 to 5 cm, 51 g kg−1 at 5 to 15 cm, 42 g kg−1 at 15 to 30 cm, 29 g kg−1 at 30 to 60 cm, 17 g kg−1 at 60 to 100 cm, and 11 g kg−1 at 100 to 200 cm. Model validation, withholding 25% of pedons, showed R2 values of 0.70, 0.73, 0.75, 0.65, 0.56, and 0.29 for six depths, respectively. Two future temperature and precipitation for climate change scenarios, representative concentration pathways RCP4.5 and RCP8.5 from the NASA GISS‐E2‐R models, were considered in predicting SOC in 2050 and 2080. We found that central Chile would experience a loss of SOC in the depth range of 0 to 30 cm, averaging 9.7% for RCP4.5 and 12.9% for the RCP8.5 scenarios by the year 2050, with additional decreases of 8% in the RCP4.5 scenario and 16.5% under RCP8.5 by 2080.
Core Ideas
We mapped soil organic C concentration in current and future climates.
Soil organic C in central Chile is affected by changes in rainfall and temperature.
We discuss the rescue and use of legacy data for digital soil mapping.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
OBJECTIVESMajor depressive disorder (MDD) is one of the most disabling mental illnesses and it has a significant impact on society. This review aims to provide updated scientific evidence about the ...epidemiology of MDD. METHODSA systematic literature review of the PubMed and MEDLINE databases was performed to identify articles on the prevalence of MDD and its correlates. The search was restricted to manuscripts published between January 2001 and December 2018. RESULTSSixty-three articles were included in the review. The lifetime prevalence of MDD ranged from 2 to 21%, with the highest rates found in some European countries and the lowest in some Asian countries. The main sociodemographic correlates were separated/divorced marital status and female gender. Child abuse, intimate partner violence, and comorbidity with other physical and mental disorders also were consistently associated with MDD across the reviewed studies. CONCLUSIONSMDD is a highly prevalent condition worldwide. There are remarkable interregional differences in the disorder's prevalence, as well as in certain sociodemographic correlates. MDD is also highly comorbid with physical and mental health problems.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Copper mining has led to Cu pollution in agricultural soils. In this report, the effects of Cu pollution on bacterial communities of agricultural soils from Valparaiso region, central Chile, were ...studied. Denaturing gradient gel electrophoresis (DGGE) of the 16S rRNA genes was used for the characterization of bacterial communities from Cu-polluted and non-polluted soils. Cu-resistant bacterial strains were isolated from Cu-polluted soils and characterized.
DGGE showed a similar high number of bands and banding pattern of the bacterial communities from Cu-polluted and non-polluted soils. The presence of copA genes encoding the multi-copper oxidase that confers Cu-resistance in bacteria was detected by PCR in metagenomic DNA from the three Cu-polluted soils, but not in the non-polluted soil. The number of Cu-tolerant heterotrophic cultivable bacteria was significantly higher in Cu-polluted soils than in the non-polluted soil. Ninety two Cu-resistant bacterial strains were isolated from three Cu-polluted agricultural soils. Five isolated strains showed high resistance to copper (MIC ranged from 3.1 to 4.7 mM) and also resistance to other heavy metals. 16S rRNA gene sequence analyses indicate that these isolates belong to the genera Sphingomonas, Stenotrophomonas and Arthrobacter. The Sphingomonas sp. strains O12, A32 and A55 and Stenotrophomonas sp. C21 possess plasmids containing the Cu-resistance copA genes. Arthrobacter sp. O4 possesses the copA gene, but plasmids were not detected in this strain. The amino acid sequences of CopA from Sphingomonas isolates (O12, A32 and A55), Stenotrophomonas strain (C21) and Arthrobacter strain (O4) are closely related to CopA from Sphingomonas, Stenotrophomonas and Arthrobacter strains, respectively.
This study suggests that bacterial communities of agricultural soils from central Chile exposed to long-term Cu-pollution have been adapted by acquiring Cu genetic determinants. Five bacterial isolates showed high copper resistance and additional resistance to other heavy metals. Detection of copA gene in plasmids of four Cu-resistant isolates indicates that mobile genetic elements are involved in the spreading of Cu genetic determinants in polluted environments.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Group 2 innate lymphoid cells (ILC2s) regulate inflammation and immunity in mammalian tissues
. Although ILC2s are found in cancers of these tissues
, their roles in cancer immunity and immunotherapy ...are unclear. Here we show that ILC2s infiltrate pancreatic ductal adenocarcinomas (PDACs) to activate tissue-specific tumour immunity. Interleukin-33 (IL33) activates tumour ILC2s (TILC2s) and CD8
T cells in orthotopic pancreatic tumours but not heterotopic skin tumours in mice to restrict pancreas-specific tumour growth. Resting and activated TILC2s express the inhibitory checkpoint receptor PD-1. Antibody-mediated PD-1 blockade relieves ILC2 cell-intrinsic PD-1 inhibition to expand TILC2s, augment anti-tumour immunity, and enhance tumour control, identifying activated TILC2s as targets of anti-PD-1 immunotherapy. Finally, both PD-1
TILC2s and PD-1
T cells are present in most human PDACs. Our results identify ILC2s as anti-cancer immune cells for PDAC immunotherapy. More broadly, ILC2s emerge as tissue-specific enhancers of cancer immunity that amplify the efficacy of anti-PD-1 immunotherapy. As ILC2s and T cells co-exist in human cancers and share stimulatory and inhibitory pathways, immunotherapeutic strategies to collectively target anti-cancer ILC2s and T cells may be broadly applicable.
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FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
In this paper, the transient analysis of an AlGaN/GaN high-electron mobility transistor (HEMT) device is presented. Drain-current dispersion effects are investigated when gate or drain voltages are ...pulsed. Gate-lag and drain-lag turn-on measurements are analyzed, revealing clear mechanisms of current collapse and related dispersion effects. Numerical 2-D transient simulations considering surface traps effects in a physical HEMT model have also been carried out. A comparison between experimental and theoretical results is shown. The presence of donor-type traps acting as hole traps, due to their low energy level of 0.25 eV relative to the valence band, with densities >1e20 cm -3 (>5e12 cm -2 ), uniformly distributed at the HEMT surface, and interacting with the free holes that accumulated at the top surface due to piezoelectric fields, accounts for the experimentally observed effects. Time constants next to 10 ms are deduced. Some additional features in the measured transient currents, with faster time constants, could not be associated with surface states
Cancer immunoediting
is a hallmark of cancer
that predicts that lymphocytes kill more immunogenic cancer cells to cause less immunogenic clones to dominate a population. Although proven in mice
, ...whether immunoediting occurs naturally in human cancers remains unclear. Here, to address this, we investigate how 70 human pancreatic cancers evolved over 10 years. We find that, despite having more time to accumulate mutations, rare long-term survivors of pancreatic cancer who have stronger T cell activity in primary tumours develop genetically less heterogeneous recurrent tumours with fewer immunogenic mutations (neoantigens). To quantify whether immunoediting underlies these observations, we infer that a neoantigen is immunogenic (high-quality) by two features-'non-selfness' based on neoantigen similarity to known antigens
, and 'selfness' based on the antigenic distance required for a neoantigen to differentially bind to the MHC or activate a T cell compared with its wild-type peptide. Using these features, we estimate cancer clone fitness as the aggregate cost of T cells recognizing high-quality neoantigens offset by gains from oncogenic mutations. With this model, we predict the clonal evolution of tumours to reveal that long-term survivors of pancreatic cancer develop recurrent tumours with fewer high-quality neoantigens. Thus, we submit evidence that that the human immune system naturally edits neoantigens. Furthermore, we present a model to predict how immune pressure induces cancer cell populations to evolve over time. More broadly, our results argue that the immune system fundamentally surveils host genetic changes to suppress cancer.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chronic neuroinflammation has been implicated in neurodegenerative disease pathogenesis. A key feature of neuroinflammation is neuronal loss and glial activation, including microglia and astrocytes. ...4R‐cembranoid (4R) is a natural compound that inhibits hippocampal pro‐inflammatory cytokines and increases memory function in mice. We used the lipopolysaccharide (LPS) injection model to study the effect of 4R on neuronal density and microglia and astrocyte activation. C57BL/6J wild‐type mice were injected with LPS (5 mg/kg) and 2 h later received either 4R (6 mg/kg) or vehicle. Mice were sacrificed after 72 h for analysis of brain pathology. Confocal images of brain sections immunostained for microglial, astrocyte, and neuronal markers were used to quantify cellular hippocampal phenotypes and neurons. Hippocampal lysates were used to measure the expression levels of neuronal nuclear protein (NeuN), inducible nitrous oxide synthase (iNOS), arginase‐1, thrombospondin‐1 (THBS1), glial cell‐derived neurotrophic factor (GDNF), and orosomucoid‐2 (ORM2) by western blot. iNOS and arginase‐1 are widely used protein markers of pro‐ and anti‐inflammatory microglia, respectively. GDNF promotes neuronal survival, and ORM2 and THBS1 are astrocytic proteins that regulate synaptic plasticity and inhibit microglial activation. 4R administration significantly reduced neuronal loss and the number of pro‐inflammatory microglia 72 h after LPS injection. It also decreased the expression of the pro‐inflammatory protein iNOS while increasing arginase‐1 expression, supporting its anti‐inflammatory role. The protein expression of THBS1, GDNF, and ORM2 was increased by 4R. Our data show that 4R preserves the integrity of hippocampal neurons against LPS‐induced neuroinflammation in mice.
4R‐cembranoid is a natural compound that protects neurons against LPS‐induced neuroinflammation by reducing the number of pro‐inflammatory microglia and by promoting the secretion of astrocytic neuroprotective factors in the mice hippocampus.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Alzheimer's disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β ...peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objective Depression and obesity are two conditions with great impact over global health. This is mainly due to their high prevalence and the morbidity and mortality associated to both. The main aim ...of the present systematic review is to study the association between obesity and depression and the prognostic implications derived from it.Methods A literature review was performed in the PUBMED database. 18 articles were found (9 cross-sectional studies, 6 longitudinal studies and 3 clinical trials), which were reviewed by critical reading after which a summary of the main conclusions was written.Results These selected articles confirmed that there is indeed a link between depression and obesity, although there are doubts as to the significance of this relationship. Depression is a risk factor for obesity, especially atypical depression and in African-American adolescent males. Obesity is a risk factor for depression, especially in women and for recurrent depressive disorder. The comorbidity between obesity and depression is a risk factor for a bad prognosis illness.Conclusion The relationship between both disorders has been analysed in scientific literature, obtaining significant associations but also contradictory results. The most current data demonstrates that there is a relationship between both entities, although there is no unanimity when it comes to establishing the meaning of this association.
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