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Figure S4. Hippocampus RNA-seq significantly enriched KEGG pathway annotations. KEGG pathways significantly enriched in genes that were differentially expressed in hippocampus of CORT + DFP exposed mice. (CSV 3Â kb)

Antimicrobial peptides (AP) are important components of the innate immune system, yet little is known about their expression and function in the brain. Our previous work revealed upregulated gene expression of cathelicidin-related AP (CRAMP) following bacterial meningitis in primary rat glial cells as well as bactericidal activity against frequent meningitis-causing bacteria. However, the effect of cathelicidin expression on the progression of inflammation and mortality in bacterial meningitis remains unknown. Therefore, we used CRAMP-deficient mice to investigate the effect of CRAMP on bacterial growth, inflammatory responses and mortality in meningitis. Meningitis was induced by intracerebral injection of type 3 Streptococcus pneumoniae. The degree of inflammation was analyzed in various brain regions by means of immunohistochemistry and real-time RT-PCR. CRAMP deficiency led to a higher mortality rate that was associated with increased bacterial titers in the cerebellum, blood and spleen as well as decreased meningeal neutrophil infiltration. CRAMP-deficient mice displayed a higher degree of glial cell activation that was accompanied by a more pronounced proinflammatory response. Taken together, this work provides insight into the important role of CRAMP as part of the innate immune defense against pathogens in bacterial CNS infections. © 2013 S. Karger AG, Basel

Perception adapts to mismatching multisensory information, both when different cues appear simultaneously and when they appear sequentially. While both multisensory integration and adaptive trial-by-trial recalibration are central for behavior, it remains unknown whether they are mechanistically linked and arise from a common neural substrate. To relate the neural underpinnings of sensory integration and recalibration, we measured whole-brain magnetoencephalography while human participants performed an audio-visual ventriloquist task. Using single-trial multivariate analysis, we localized the perceptually-relevant encoding of multisensory information within and between trials. While we found neural signatures of multisensory integration within temporal and parietal regions, only medial superior parietal activity encoded past and current sensory information and mediated the perceptual recalibration within and between trials. These results highlight a common neural substrate of sensory integration and perceptual recalibration, and reveal a role of medial parietal regions in linking present and previous multisensory evidence to guide adaptive behavior. PARK_KAYSER_RecalMEG_2019Please see README file.

EFA with raters left in sample 1

The purpose of this study was to evaluate cerebrovascular reactivity (CVR) of major arterial vascular territories, particularly in the contralateral hemodynamically unaffected hemisphere, in patients with unilateral internal carotid artery (ICA) steno-occlusive disease compared to control subjects with risk factors for cerebrovascular disease. Methods: In this retrospective observational study, twenty-seven patients with right-sided unilateral ICA steno-occlusive disease (age range, 25 to 91 years; 17 males) and twenty-one patients with left-sided unilateral ICA steno-occlusive disease (age range, 24 to 83 years; 14 males) and 41 control subjects were studied. CVR was quantitated as the change in blood oxygen level dependent (BOLD) MRI signal (as a surrogate of cerebral blood flow), in response to a consistently applied step change in the arterial partial pressure of carbon dioxide (PaCO2). The CVR of each major arterial vascular territory was assessed in the ipsilateral hemodynamically affected hemisphere and compared to the corresponding territory in the contralateral hemisphere. Results: In patients, a significant reduction in CVR was observed in the ipsilateral anterior circulation compared to that of the corresponding territory on the contralateral side (0.027 ± 0.083 vs. 0.109 ± 0.066% BOLD change/​mm Hg, p < 0.0001) and to controls (0.195 ± 0.054% BOLD change/mm Hg, p < 0.0001). The CVR of the contralateral anterior circulation was reduced on average by 50% compared to controls (p < 0.0001). Conclusions: The implication of these findings is that unilateral carotid stenosis affects the vascular reserve of both sides of the brain compared to control subjects. This indicates that the collateral blood flow support from the contralateral to the ipsilateral hemisphere comes at a cost of reduced reserve capacity in the contralateral hemisphere. The findings suggest that there may be a reduction in functional hyperemia associated with neuronal activation, not only affecting the hemisphere ipsilateral to an occlusion, but also the hemisphere contralateral to an occlusion. It remains to be determined if ‘stealing' from the ‘rich' to support the ‘poor' has clinical consequences over the long term.

Kawamichi H*, Sugawara SK, Hamano YH, Kitada R, Nakagawa E, Kochiyama T, Sadato N (2018) Neural correlates underlying change in state self-esteem Sci Rep, 8, 1798

The present study aimed to investigate the expression, role, and underlying mechanism of action of sirtuin 1 (SIRT1) in congenital hypothyroidism (CH). A CH model was established in rats, and neuronal cells were isolated from the hippocampal tissues of normal rats. Free thyroxine (fT4) and thyroid-Stimulating hormone (TSH) concentrations were determined to confirm CH model conduction. The cognitive behavior of rats with CH was examined using open field and forced swimming tests. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting were used to detect the expression levels of SIRT1, p53, B-cell lymphoma-extra-large (Bcl-xl), Bcl-2-associated X (Bax), and cytochrome c in the hippocampal tissues and neuronal cells. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and flow cytometry were performed to evaluate cell viability and apoptosis, respectively. The results revealed that SIRT1 was expressed at low levels in the hippocampal tissues of rats with CH. Moreover, overexpression of SIRT1 in the hippocampal tissues of rats with CH and improved rat behavior, while reducing the CH-induced nerve cell apoptosis. In addition, this overexpression increased the viability, inhibited apoptosis, and reduced the expression of p53, Bax, and cytochrome c, while increasing the expression of Bcl-xl in cultured neurons. In contrast, SIRT1-small interfering RNA exhibited the opposite effects in cultured neurons. In conclusion, SIRT1 plays a role in the occurrence and development of CH by regulating nerve cell apoptosis.

L-Dopa and dopamine are important pathway intermediates toward the synthesis of catecholamine such as epinephrine and norepinephrine from amino acid L-tyrosine. Dopamine, secreted from dopaminergic nerve cells, serves as an important neurotransmitter. We report the synthesis of dopamine by extending the aromatic amino acid pathway of Escherichia coli DH5α by the expression of 4-hydroxyphenylacetate-3-hydrolase (HpaBC) from E. coli and an engineered dopa decarboxylase (DDC) from pig kidney cell. The activity of HpaBC and DDC require 200 µM iron supplementation and 50 µM vitamin B6, respectively as additives to the growth media. The maximum concentration of L-dopa and dopamine obtained from the broth was around 26 and 27 mg/L after 24 hr of separate shake flask studies. We observed that in the presence of dopamine synthesized in vivo host growth was remarkably enhanced. These observations lead us to an interesting finding about the role of these catecholamines on bacterial growth. It is clear that synthesis of dopamine in vivo actually promotes growth much efficiently as compared to when dopamine is added to the system from outside. From HPLC and GC–MS data it was further observed that L-dopa was stable within the observable time of experiments whereas dopamine actually was subjected to degradation via oxidation and host consumption.

This systematic review aimed to explore the perspectives of healthcare, exercise, and fitness professionals working with people post-stroke regarding the factors affecting the implementation of aerobic exercise after stroke. OVID SP MEDLINE, OVID SP EMBASE, and CINAHL were searched from inception to December 2018 using a combination of search terms with synonyms of stroke, aerobic exercise and barriers/facilitators. Studies focusing on the factors affecting implementation of aerobic exercise after stroke from staff perspectives were included with no restriction on the types of study design. For inclusivity, a broad definition of aerobic exercise was used. Review authors independently extracted data from included studies using domains from the Consolidated Framework for Implementation Research, then synthesised using a framework synthesis approach. Retrospective automated screening was conducted using Rayyan software. Twenty studies were included. Four reported on implementation of aerobic exercise, sixteen on general exercise interventions, all post-stroke. Factors identified as influencing implementation of aerobic exercise after stroke included professionals’ self-efficacy and knowledge about stroke, patients’ needs, communication and collaboration within and between organisations and resources such as equipment, staff and training. Key factors influencing the implementation of aerobic exercise after stroke included characteristics of the staff and intervention and system-level issues, some of which are modifiable. Further research should evaluate strategies which specifically target these modifiable factors to facilitate implementation in practice.IMPLICATIONS FOR REHABILITATIONAerobic exercise after stroke is an effective intervention but there are challenges to implementation from a staff and system perspective.Any changes to the identified factors should be tailored to suit the staff group and setting.Provision of training and knowledge-sharing could improve staff’s confidence in the prescription and delivery of aerobic exercise after stroke though other implementation strategies should also be considered. Aerobic exercise after stroke is an effective intervention but there are challenges to implementation from a staff and system perspective. Any changes to the identified factors should be tailored to suit the staff group and setting. Provision of training and knowledge-sharing could improve staff’s confidence in the prescription and delivery of aerobic exercise after stroke though other implementation strategies should also be considered.