Comparison of Computerized Cardiotocography Parameters between Male and Female Fetuses

Fetal sex has been identified as an important factor influencing pregnancy outcomes, but its impact on fetal heart rate (FHR) variability in uncomplicated pregnancies is still unclear. The objective of the study was to assess short-term variability (STV) and other computerized cardiotocography (cCTG) parameters in relation to fetal sex during fetal antepartum surveillance. We retrospective compared cCTG parameters of male and female fetuses in uncomplicated singleton pregnancies at term. In addition to univariate analysis, a multivariate analysis was performed taking into account maternal characteristics. A total of 689 cCTG recordings were analyzed: 335 from male fetuses and 354 from female fetuses. Analysis of cCTG results by fetal sex showed no significant difference in percentage of signal loss, number of contractions, movements, accelerations and decelerations, long-term variability (LTV), and STV at both uni-and multivariate analysis. There was a statistically significant difference for baseline FHR at the univariate analysis, which was not confirmed by a multivariate analysis. Our results suggest that fetal sex did not affect cCTG parameters in uncomplicated term singleton pregnancies, and therefore it does not need to be taken into account when interpreting cCTG in physiological conditions

Regular Physical Exercise Modulates Iron Homeostasis in the 5xFAD Mouse Model of Alzheimer’s Disease

Dysregulation of brain iron metabolism is one of the pathological features of aging and Alzheimer’s disease (AD), a neurodegenerative disease characterized by progressive memory loss and cognitive impairment. While physical inactivity is one of the risk factors for AD and regular exercise improves cognitive function and reduces pathology associated with AD, the underlying mechanisms remain unclear. The purpose of the study is to explore the effect of regular physical exercise on modulation of iron homeostasis in the brain and periphery of the 5xFAD mouse model of AD. By using inductively coupled plasma mass spectrometry and a variety of biochemical techniques, we measured total iron content and level of proteins essential in iron homeostasis in the brain and skeletal muscles of sedentary and exercised mice. Long-term voluntary running induced redistribution of iron resulted in altered iron metabolism and trafficking in the brain and increased iron content in skeletal muscle. Exercise reduced levels of cortical hepcidin, a key regulator of iron homeostasis, coupled with interleukin-6 (IL-6) decrease in cortex and plasma. We propose that regular exercise induces a reduction of hepcidin in the brain, possibly via the IL-6/STAT3/JAK1 pathway. These findings indicate that regular exercise modulates iron homeostasis in both wild-type and AD mice

CO2FIX V2.0 : manual of a modeling framework for quantifying carbon sequestration in forest ecosystems and wood products

This reports presents a manual of the CO2FIX V 2.0 model. CO2FIX V 2.0 is a simple bookkeeping model that converts volumetric net annual increment data (and additional parameters) to annual carbon stocks and fluxes of the forest ecosystem-soil-wood products chain. It calculates on the hectare scale with time steps of one year. This Version 2.0 is a hectare scale model which was improved on the ability to simulate multi-species and uneven aged stands in multiple cohorts (e.g. selective tropical selective logging systems, and agroforestry systems); the ability to parametrize the growth also by stand density; the ability to deal with inter cohort competition; harvesting, allocation, processing lines, and end-of-life disposal of harvested wood; soil dynamics; the ability to deal with a wider variety of forest types including agro-forestry systems, selective logging systems, and post harvesting mortality; output viewing charts

A Retrospective Stated Preference Approach to Assessment of Coastal Infrastructure Investments: An Application to Barbados

Ex-post economic impact evaluations are standard requirements for loans and grants from multilateral international development institutions. In many cases, however, lack of sufficient baseline or historical data, or the very nature of the investment itself renders orthodox economic impact evaluation approaches unviable. Nonetheless, evaluations are required to provide an indication of the benefits generated by the investment and insights for future program design. Addressing this challenge, this paper develops an ecosystem service, retrospective stated preferences approach to assess the benefits of a coastal infrastructure investment in Barbados. Results show that the investment generated cultural and aesthetic ecosystem service benefits for tourists and residents, and that local businesses derived value and avoided some damage costs from the enhancement of regulatory ecosystem services. The approach is versatile facing data constraints and generates policy-relevant information to support decisions to scale up interventions, catalyze additional investment, and provide data on user preferences that can be incorporated in the design of future interventions

Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation

Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.Peer reviewe

Synergies among social safeguards in FLEGT and REDD+ in Cameroon

Synergies among social safeguards in FLEGT and REDD plus in CameroonPeer reviewe

Intracerebral overexpression of miR-669c is protective in mouse ischemic stroke model by targeting MyD88 and inducing alternative microglial/macrophage activation

Background Ischemic stroke is a devastating disease without a cure. The available treatments for ischemic stroke, thrombolysis by tissue plasminogen activator, and thrombectomy are suitable only to a fraction of patients and thus novel therapeutic approaches are urgently needed. The neuroinflammatory responses elicited secondary to the ischemic attack further aggravate the stroke-induced neuronal damage. It has been demonstrated that these responses are regulated at the level of non-coding RNAs, especially miRNAs. Methods We utilized lentiviral vectors to overexpress miR-669c in BV2 microglial cells in order to modulate their polarization. To detect whether the modulation of microglial activation by miR-669c provides protection in a mouse model of transient focal ischemic stroke, miR-669c overexpression was driven by a lentiviral vector injected into the striatum prior to induction of ischemic stroke. Results Here, we demonstrate that miR-669c-3p, a member of chromosome 2 miRNA cluster (C2MC), is induced upon hypoxic and excitotoxic conditions in vitro and in two different in vivo models of stroke. Rather than directly regulating the neuronal survival in vitro, miR-669c is capable of attenuating the microglial proinflammatory activation in vitro and inducing the expression of microglial alternative activation markers arginase 1 (Arg1), chitinase-like 3 (Ym1), and peroxisome proliferator-activated receptor gamma (PPAR-gamma). Intracerebral overexpression of miR-669c significantly decreased the ischemia-induced cell death and ameliorated the stroke-induced neurological deficits both at 1 and 3 days post injury (dpi). Albeit miR-669c overexpression failed to alter the overall Iba1 protein immunoreactivity, it significantly elevated Arg1 levels in the ischemic brain and increased colocalization of Arg1 and Iba1. Moreover, miR-669c overexpression under cerebral ischemia influenced several morphological characteristics of Iba1 positive cells. We further demonstrate the myeloid differentiation primary response gene 88 (MyD88) transcript as a direct target for miR-669c-3p in vitro and show reduced levels of MyD88 in miR-669c overexpressing ischemic brains in vivo. Conclusions Collectively, our data provide the evidence that miR-669c-3p is protective in a mouse model of ischemic stroke through enhancement of the alternative microglial/macrophage activation and inhibition of MyD88 signaling. Our results accentuate the importance of controlling miRNA-regulated responses for the therapeutic benefit in conditions of stroke and neuroinflammation.Peer reviewe

HX600, a synthetic agonist for RXR-Nurr1 heterodimer complex, prevents ischemia-induced neuronal damage

Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A-family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown. Here we show for the first time that an agonist for the dimeric transcription factor Nurr1/retinoid X receptor (RXR), HX600, reduces microglia expressed proinflammatory mediators and prevents inflammation induced neuronal death in in vitro co-culture model of neurons and microglia. Importantly, HX600 was protective in a mouse model of permanent middle cerebral artery occlusion and alleviated the stroke induced motor deficits. Along with the anti-inflammatory capacity of HX600 in vitro, treatment of ischemic mice with HX600 reduced ischemia induced Iba-1, p38 and TREM2 immunoreactivities, protected endogenous microglia from ischemia induced death and prevented leukocyte infiltration. These anti-inflammatory functions were associated with reduced levels of brain lysophosphatidylcholines (lysoPCs) and acylcarnitines, metabolites related to proinflammatory events. These data demonstrate that HX600 driven Nurr1 activation is beneficial in ischemic stroke and propose that targeting Nurr1 is a novel candidate for conditions involving neuroinflammatory component.Peer reviewe

An arylthiazyne derivative is a potent inhibitor of lipid peroxidation and ferroptosis providing neuroprotection in vitro and in vivo

Lipid peroxidation-initiated ferroptosis is an iron-dependent mechanism of programmed cell death taking place in neurological diseases. Here we show that a condensed benzo[b]thiazine derivative small molecule with an arylthiazine backbone (ADA-409-052) inhibits tert-Butyl hydroperoxide (TBHP)-induced lipid peroxidation (LP) and protects against ferroptotic cell death triggered by glutathione (GSH) depletion or glutathione peroxidase 4 (GPx4) inhibition in neuronal cell lines. In addition, ADA-409-052 suppresses pro-inflammatory activation of BV2 microglia and protects N2a neuronal cells from cell death induced by pro-inflammatory RAW 264.7 macrophages. Moreover, ADA-409-052 efficiently reduces infarct volume, edema and expression of pro-inflammatory genes in a mouse model of thromboembolic stroke. Targeting ferroptosis may be a promising therapeutic strategy in neurological diseases involving severe neuronal death and neuroinflammation.Peer reviewe

A transgenic mouse model for monitoring oxidative stress

Oxidative stress conditions enhance the production of reactive oxygen species resulting from a variety of stimuli, and are associated with various human diseases, including neurodegenerative disorders, inflammation, and various cancers. Though such associations have been closely studied using animal models, there has been no in vivo system for monitoring oxidative stress. We have developed an oxidative stress indicator that is dually regulated by induction at the transcriptional level, and by protein stabilisation at the post-translational level in Keap1-Nrf2 pathway. In vitro, our indicator elicited an intense and specific signal to oxidative stress among various agents, in a Keap1-Nrf2-dependent manner. Moreover, the transgenic animal expressing the indicator exhibited significant signals upon oxidative stress. These results indicate the usefulness of our system as an indicator of oxidative stress both in vitro and in vivo