Inflammation is emerging as a critical mechanism underlying neurological disorders of various etiologies, yet its role in altering brain function as a consequence of neuroinfectious disease remains ...unclear. Although acute alterations in mental status due to inflammation are a hallmark of central nervous system (CNS) infections with neurotropic pathogens, post-infectious neurologic dysfunction has traditionally been attributed to irreversible damage caused by the pathogens themselves. More recently, studies indicate that pathogen eradication within the CNS may require immune responses that interfere with neural cell function and communication without affecting their survival. In this Review we explore inflammatory processes underlying neurological impairments caused by CNS infection and discuss their potential links to established mechanisms of psychiatric and neurodegenerative diseases.
Neurotropic RNA virus infections cause a major neurological disease burden. Due to the morbidity and mortality rates of viral encephalitides worldwide, there is a need to develop clinical treatments. ...Features of the central nervous system (CNS), including interconnected cell types and limited regeneration, provide unique challenges. Viral encephalitis and antiviral immunity can disrupt the CNS environment, leaving patients with poor neurological outcomes despite virologic control. The cellular mechanism(s) underlying neurological recovery are not fully understood, but involve neuroimmune interactions that, until recently, primarily focused on microglia. With increasing evidence that astrocytes also have significant roles in inflammatory responses to viruses, here we summarize recent astrocyte contributions to acute virologic control and neurological impairments during recovery from viral infection.
Neurotropic RNA viruses invade the CNS, often eliciting serious chronic neurological impairments.
Astrocytes are activated during acute viral infection and can persist over a long period of time.
Astrocyte activation during acute infection is vital for viral control and clearance.
However, persistent activation of astrocytes has been implicated as a cause of long-term neurological impairments after viral infection.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The concept of immune privilege of the central nervous system (CNS) has dominated the study of inflammatory processes in the brain. However, clinically relevant models have highlighted that innate ...pathways limit pathogen invasion of the CNS and adaptive immunity mediates control of many neural infections. As protective responses can result in bystander damage, there are regulatory mechanisms that balance protective and pathological inflammation, but these mechanisms might also allow microbial persistence. The focus of this review is to consider the host-pathogen interactions that influence neurotropic infections and to highlight advances in our understanding of innate and adaptive mechanisms of resistance as key determinants of the outcome of CNS infection. Advances in these areas have broadened our comprehension of how the immune system functions in the brain and can readily overcome immune privilege.
The CNS utilizes multiple mechanisms to restrict microbial entry but there are also innate and adaptive mechanisms that control pathogens that access this immune privileged site. Klein and Hunter review the pathogen interactions with the blood brain barrier and resident glial populations that govern the outcome of CNS infection, as well as the immune mechanisms that dictate protective and pathological responses in the brain.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Zika virus (ZIKV) infection in pregnant women causes intrauterine growth restriction, spontaneous abortion, and microcephaly. Here, we describe two mouse models of placental and fetal disease ...associated with in utero transmission of ZIKV. Female mice lacking type I interferon signaling (Ifnar1−/−) crossed to wild-type (WT) males produced heterozygous fetuses resembling the immune status of human fetuses. Maternal inoculation at embryonic day 6.5 (E6.5) or E7.5 resulted in fetal demise that was associated with ZIKV infection of the placenta and fetal brain. We identified ZIKV within trophoblasts of the maternal and fetal placenta, consistent with a trans-placental infection route. Antibody blockade of Ifnar1 signaling in WT pregnant mice enhanced ZIKV trans-placental infection although it did not result in fetal death. These models will facilitate the study of ZIKV pathogenesis, in utero transmission, and testing of therapies and vaccines to prevent congenital malformations.
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•Establishment of an in utero transmission model of ZIKV infection•ZIKV infects placental cells and results in intrauterine growth restriction•ZIKV infection and injury of the fetal brain is observed•ZIKV infection of fetuses can occur by a trans-placental route
Zika virus infection of mice early in pregnancy results in infection of the placenta and fetal brain, causing a fetal syndrome that resembles the intrauterine growth restriction and spontaneous abortion observed in ZIKV-infected pregnant women.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
How does the brain maintain fear within an adaptive range? We found that the insular cortex acts as a state-dependent regulator of fear that is necessary to establish an equilibrium between the ...extinction and maintenance of fear memories in mice. Whereas insular cortex responsiveness to fear-evoking cues increased with their certainty to predict harm, this activity was attenuated through negative bodily feedback that arose from heart rate decelerations during freezing. Perturbation of body-brain communication by vagus nerve stimulation disrupted the balance between fear extinction and maintenance similar to insular cortex inhibition. Our data reveal that the insular cortex integrates predictive sensory and interoceptive signals to provide graded and bidirectional teaching signals that gate fear extinction and illustrate how bodily feedback signals are used to maintain fear within a functional equilibrium.
Starting from a model of impaired response inhibition and salience attribution for addictive behaviour we investigated whether obese participants show a greater impairment of inhibitory control in ...response to food-associated cues compared with neutral stimuli and whether this is seen in normal-weight control subjects. In addition, we questioned whether an attentional bias towards food-associated cues can be observed in an early stage of information processing.
Control-group study including the administration of behavioural tasks (that is, go/no-go task with food-associated and neutral words, visual dot probe task with food-associated and neutral pictures) and self-reported measures of eating behaviour and impulsivity.
Although self-reported measures indicated disinhibition of eating behaviour of obese patients, we found that food-associated stimuli induced an impairment of inhibitory control in both obese participants as well as normal-weight controls. Results from the visual dot-probe task indicated that food-associated cues did not modulate attention allocation in a very early stage of information processing, which suggests that the incentive salience of food-associated stimuli might be lower than that of drug-associated cues.
These findings are not in line with hypotheses derived from models of addictive behaviour and call into question that an impairment of inhibitory control in response to food-associated cues and salience attribution might be at the core of obesity. Future studies using larger sample sizes and refined experimental procedures are warranted to further investigate mechanisms controlling food intake in obesity.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Medical image registration is an important task in medical image processing. It refers to the process of aligning data sets, possibly from different modalities (e.g., magnetic resonance and computed ...tomography), different time points (e.g., follow-up scans), and/or different subjects (in case of population studies). A large number of methods for image registration are described in the literature. Unfortunately, there is not one method that works for all applications. We have therefore developed elastix, a publicly available computer program for intensity-based medical image registration. The software consists of a collection of algorithms that are commonly used to solve medical image registration problems. The modular design of elastix allows the user to quickly configure, test, and compare different registration methods for a specific application. The command-line interface enables automated processing of large numbers of data sets, by means of scripting. The usage of elastix for comparing different registration methods is illustrated with three example experiments, in which individual components of the registration method are varied.
Manufacturers of photovoltaic panels typically provide electrical parameters at only one operating condition. Photovoltaic panels operate over a large range of conditions so the manufacturer’s ...information is not sufficient to determine their overall performance. Designers need a reliable tool to predict energy production from a photovoltaic panel under all conditions in order to make a sound decision on whether or not to incorporate this technology. A model to predict energy production has been developed by Sandia National Laboratory, but it requires input data that are normally not available from the manufacturer. The five-parameter model described in this paper uses data provided by the manufacturer, absorbed solar radiation and cell temperature together with semi-empirical equations, to predict the current–voltage curve. This paper indicates how the parameters of the five-parameter model are determined and compares predicted current–voltage curves with experimental data from a building integrated photovoltaic facility at the National Institute of Standards and Technology (NIST) for four different cell technologies (single crystalline, poly crystalline, silicon thin film, and triple-junction amorphous). The results obtained with the Sandia model are also shown. The predictions from the five-parameter model are shown to agree well with both the Sandia model results and the NIST measurements for all four cell types over a range of operating conditions. The five-parameter model is of interest because it requires only a small amount of input data available from the manufacturer and therefore it provides a valuable tool for energy prediction. The predictive capability could be improved if manufacturer’s data included information at two radiation levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
The Coronavirus Disease 2019 (COVID-19) pandemic has threatened global mental health, both indirectly via disruptive societal changes and directly via neuropsychiatric sequelae after SARS-CoV-2 ...infection. Despite a small increase in self-reported mental health problems, this has (so far) not translated into objectively measurable increased rates of mental disorders, self-harm or suicide rates at the population level. This could suggest effective resilience and adaptation, but there is substantial heterogeneity among subgroups, and time-lag effects may also exist. With regard to COVID-19 itself, both acute and post-acute neuropsychiatric sequelae have become apparent, with high prevalence of fatigue, cognitive impairments and anxiety and depressive symptoms, even months after infection. To understand how COVID-19 continues to shape mental health in the longer term, fine-grained, well-controlled longitudinal data at the (neuro)biological, individual and societal levels remain essential. For future pandemics, policymakers and clinicians should prioritize mental health from the outset to identify and protect those at risk and promote long-term resilience.
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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
Climate change is a threat to marine ecosystems and the services they provide, and reducing fishing pressure is one option for mitigating the overall consequences for marine biota. We used a ...minimally realistic ecosystem model to examine how projected effects of ocean warming on the growth of Antarctic krill, Euphausia superba, might affect populations of krill and dependent predators (whales, penguins, seals, and fish) in the Scotia Sea. We also investigated the potential to mitigate depletion risk for predators by curtailing krill fishing at different points in the 21st century. The projected effects of ocean warming on krill biomass were strongest in the northern Scotia Sea, with a ≥40% decline in the mass of individual krill. Projections also suggest a 25% chance that krill biomass will fall below an established depletion threshold (75% of its unimpacted level), with consequent risks for some predator populations, especially penguins. Average penguin abundance declined by up to 30% of its unimpacted level, with up to a 50% chance of falling below the depletion threshold. Simulated krill fishing at currently permitted harvest rates further increased risks for depletion, and stopping fishing offset the increased risks associated with ocean warming in our model to some extent. These results varied by location and species group. Risk reductions at smaller spatial scales also differed from those at the regional level, which suggests that some predator populations may be more vulnerable than others to future changes in krill biomass. However, impacts on predators did not always map directly to those for krill. Our findings indicate the importance of identifying vulnerable marine populations and targeting protection measures at appropriate spatial scales, and the potential for spatially-structured management to avoid aggravating risks associated with rising ocean temperatures. This may help balance tradeoffs among marine ecosystem services in an uncertain future.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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