Differential Involvement Research Articles

Differential involvement of WRKY genes in abiotic stress tolerance of Dendrobium huoshanense

Extreme environments have adversely affected the habitats of medicinal Dendrobium species. Dendrobium huoshanense, a well-known traditional Chinese medicinal plant, is highly susceptible to abiotic stress. Evidence suggests that WRKY transcription factors play versatile roles in responding to both biotic and abiotic stressors experienced by terrestrial plants. The regulatory mechanisms underlying the stress responses of WRKY genes have been characterized for several model plants. In this study, 64 WRKY genes were identified in the D. huoshanense genome. Chromosome localization analysis showed that all the WRKY genes were anchored on the 15 pseudochromosomes, among which chromosome 5 was occupied by the highest number of WRKY genes (from DhWRKY7 to DhWRKY19), followed by chromosome 17 (from DhWRKY45 to DhWRKY53). Subcellular localization predictions indicated that most of the WRKY genes were located in the nucleus, with only a few WRKY genes localized in peroxisome, plastid, and mitochondria. Analysis of the conserved motifs and gene structure demonstrated that most genes, except for a few truncated genes, had more than two exons, and this was likely to be due to transposon insertion. A comparative genomics investigation based on the number of synteny blocks indicated the close evolutionary relationships of several orchid species, such as D. nobile, D. chrysotoxum, and G. elata, with D. huoshanense. Interspecies gene duplication events suggested that Dendrobium experienced a large-scale duplication event that included whole genome duplication and segmental duplication, and a limited number of WRKY paralogs were produced by tandem duplication. Based on the construction of a phylogenetic tree with AtWRKY nomenclature, DhWRKY genes could be categorized into three primary subfamilies. Group II could be further subdivided into five subclades. Group IIc had the highest number of WRKY genes, followed by Groups I and III. Multiple alignment of the amino acid sequences indicated that all DhWRKYs encoded a zinc-finger domain in addition to the highly conserved WRKYGQK domain, indicating their potential roles in transcriptional regulation and protein–protein interactions. Expression of most of the WRKY genes could be induced by light signals, phytohormones, and diverse abiotic stresses. Quantitative RT-PCR (qRT-PCR) and expression profiling results confirmed that the expression of WRKY genes could be induced by abscisic acid, salicylic acid, methyl jasmonate, gibberellin, and cold stress. Overall, the results of the cis-acting element analysis, expression profiling, and qRT-PCR highlighted DhWRKY42 as a key regulator involved in the regulation of jasmonic-acid-responsive genes. This study can provide valuable references for the study of WRKY genes in other Dendrobium species.

Differential involvement of the anterior and posterior hippocampus, parahippocampus, and retrosplenial cortex in making precise judgments of spatial distance and object size for remotely acquired memories of environments and objects.

The hippocampus is known to support processing of precise spatial information in recently learned environments. It is less clear, but crucial for theories of systems consolidation, to know whether it also supports processing of precise spatial information in familiar environments learned long ago and whether such precision extends to objects and numbers. In this fMRI study, we asked participants to make progressively more refined spatial distance judgments among well-known Toronto landmarks (whether landmark A is closer to landmark B or C) to examine hippocampal involvement. We also tested whether the hippocampus was similarly engaged in estimating magnitude regarding sizes of familiar animals and numbers. We found that the hippocampus was only engaged in spatial judgment. Activation was greater and lasted longer in the posterior than anterior hippocampus, which instead showed greater modulation as discrimination between spatial distances became more fine grained. These findings suggest that the anterior and posterior hippocampus have different functions which are influenced differently by estimation of differential distance. Similarly, parahippocampal-place-area and retrosplenial cortex were involved only in the spatial condition. By contrast, activation of the intraparietal sulcus was modulated by precision in all conditions. Therefore, our study supports the idea that the hippocampus and related structures are implicated in retrieving and operating even on remote spatial memories whenever precision is required, as posted by some theories of systems consolidation.

Differential Corticospinal Excitability and Cortical Functional Connectivity Modulation by Spinal Cord Transcutaneous Stimulation-based Motor Training versus Motor Training alone in Able-bodied and SCI participants: A Multiple Case Study.

Spinal cord transcutaneous stimulation (scTS) has shown its potential for boosting motor, sensory, and autonomic function recovery after a spinal cord injury. Despite the demonstrated benefits, little is known about the exact neuromodulatory mechanisms triggered by scTS and the cortex involvement in the beneficial effects observed. Here, we examine the effects of scTS-based motor training and motor training alone on sensorimotor cortical functional connectivity and corticospinal excitability in able-bodied and SCI participants.Clinical Relevance- The results show preliminary evidence of differential cortical involvement and modulation by scTS-based motor training in uninjured and spinal-cord injured individuals. A better understanding of scTS mechanisms of action could help optimize the intervention design and potentiate its benefits.

Comparative analysis of the effect of hypoxia in two different tumor cell models shows the differential involvement of PTEN control of proangiogenic pathways.

Hypoxia, low, non-physiological oxygen tension is a key regulator of tumor microenvironment, determining the pathological tumor vascularization. Alleviation of hypoxia through vessel normalization may be a promising therapeutic approach. We aimed to assess the role of low oxygen tension in PTEN-related pathways and proangiogenic response, in vitro, in two different tumor cell lines, focusing on potential therapeutic targets for tumor vessel normalization. Downregulation of PTEN in hypoxia mediates the activation of distinct mechanisms: cytoplasmic pAKT activation in melanoma and pMDM2 modulation in kidney cancer. We show that hypoxia-inducedproangiogenic potential was stronger in Renca cells than B16 F10-confirmed by a distinct secretory potential and different ability to affect endothelial cells functions. Therefore, the impact of hypoxia on PTEN-mediated regulation may determine the therapeutic targets and effectiveness of vessel normalization and intrinsic characteristics of cancer cell have to be taken into account when designing treatment.

Multi-scale structural alterations of the thalamus and basal ganglia in focal epilepsy using 7T MRI.

Focal epilepsy is characterized by repeated spontaneous seizures that originate from cortical epileptogenic zone networks (EZN). Analysis of intracerebral recordings showed that subcortical structures, and in particular the thalamus, play an important role in seizure dynamics as well, supporting their structural alterations reported in the neuroimaging literature. Nonetheless, between-patient differences in EZN localization (e.g., temporal vs. non-temporal lobe epilepsy) as well as extension (i.e., number of epileptogenic regions) might impact the magnitude as well as spatial distribution of subcortical structural changes. Here we used 7 Tesla MRI T1 data to provide an unprecedented description of subcortical morphological (volume, tissue deformation, and shape) and longitudinal relaxation (T1 ) changes in focal epilepsy patients and evaluate the impact of the EZN and other patient-specific clinical features. Our results showed variable levels of atrophy across thalamic nuclei that appeared most prominent in the temporal lobe epilepsy group and the side ipsilateral to the EZN, while shortening of T1 was especially observed for the lateral thalamus. Multivariate analyses across thalamic nuclei and basal ganglia showed that volume acted as the dominant discriminator between patients and controls, while (posterolateral) thalamic T1 measures looked promising to further differentiate patients based on EZN localization. In particular, the observed differences in T1 changes between thalamic nuclei indicated differential involvement based on EZN localization. Finally, EZN extension was found to best explain the observed variability between patients. To conclude, this work revealed multi-scale subcortical alterations in focal epilepsy as well as their dependence on several clinical characteristics.

Modeling MOG Antibody-Associated Disorder and Neuromyelitis Optica Spectrum Disorder in Animal Models: Visual System Manifestations.

Mechanisms of visual impairment in aquaporin 4 antibody (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody (MOG-IgG)-associated disorder (MOGAD) are incompletely understood. The respective impact of optic nerve demyelination and primary and secondary retinal neurodegeneration are yet to be investigated in animal models. Active MOG35-55 experimental autoimmune encephalomyelitis (EAE) was induced in C57BL/6Jrj mice, and monoclonal MOG-IgG (8-18C5, murine), recombinant AQP4-IgG (rAb-53, human), or isotype-matched control IgG (Iso-IgG, human) was administered 10 days postimmunization. Mobility impairment was scored daily. Visual acuity by optomotor reflex and ganglion cell complex thickness (GCC, 3 innermost retinal layers) by optical coherence tomography (OCT) were longitudinally assessed. Histopathology of optic nerve and retina was investigated during presymptomatic, acute, and chronic disease phases for immune cells, demyelination, complement deposition, natural killer (NK) cell, AQP4, and astrocyte involvement, retinal ganglion cells (RGCs), and Müller cell activation. Groups were compared by nonparametric tests with a p value <0.05 indicating statistical significance. Visual acuity decreased from baseline to chronic phase in MOG-IgG (mean ± standard error of the mean: 0.54 ± 0.01 to 0.46 ± 0.02 cycles/degree, p < 0.05) and AQP4-IgG EAE (0.54 ± 0.01 to 0.43 ± 0.02, cycles/degree, p < 0.05). Immune cell infiltration of optic nerves started in presymptomatic AQP4-IgG, but not in MOG-IgG EAE (5.85 ± 2.26 vs 0.13 ± 0.10 macrophages/region of interest [ROI] and 1.88 ± 0.63 vs 0.15 ± 0.06 T cells/ROI, both p < 0.05). Few NK cells, no complement deposition, and stable glial fibrillary acid protein and AQP4 fluorescence intensity characterized all EAE optic nerves. Lower GCC thickness (Spearman correlation coefficient r = -0.44, p < 0.05) and RGC counts (r = -0.47, p < 0.05) correlated with higher mobility impairment. RGCs decreased from presymptomatic to chronic disease phase in MOG-IgG (1,705 ± 51 vs 1,412 ± 45, p < 0.05) and AQP4-IgG EAE (1,758 ± 14 vs 1,526 ± 48, p < 0.01). Müller cell activation was not observed in either model. In a multimodal longitudinal characterization of visual outcome in animal models of MOGAD and NMOSD, differential retinal injury and optic nerve involvement were not conclusively clarified. Yet optic nerve inflammation was earlier in AQP4-IgG-associated pathophysiology. Retinal atrophy determined by GCC thickness (OCT) and RGC counts correlating with mobility impairment in the chronic phase of MOG-IgG and AQP4-IgG EAE may serve as a generalizable marker of neurodegeneration.

Role of KLF4/NDRG1/DRP1 axis in hypoxia-induced pulmonary hypertension

N-myc downstream regulated gene 1 (NDRG1) has recently drawn increasing attention because of its involvement in angiogenesis, cell proliferation, and differentiation. We used in vitro [human pulmonary artery smooth muscle cells (hPASMCs)] and in vivo (rat) models under hypoxic conditions and found a vital role of NDRG1 in reducing apoptosis and increasing proliferation and migration by overexpressing and knocking down NDRG1. We also proved that hypoxia induced the protein expression of dynamin-related protein 1 (DRP1) and stimulated The phosphatidylinositol-3-kinase (PI3K)/ Protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathways, and these effects were reversed by NDRG1 knockdown. The relationship between NDRG1 and DRP1 and the PI3K/Akt/mTOR pathway was further evaluated by adding mdivi-1 (DRP1 inhibitor) or LY294002 (PI3K inhibitor). NDRG1 was found to regulate the proliferation, apoptosis, and migration of hypoxia-treated hPASMCs via DRP1 and PI3K/Akt/mTOR signaling pathways. We explored the upstream regulators of NDRG1 using in vivo and in vitro hypoxia models. Hypoxia was found to upregulate and downregulate KLF transcription factor 4 (KLF4) protein expression in the cytoplasm and nucleus, respectively. Further, we showed that KLF4 regulated the proliferation and migration of hypoxia-treated hPASMCs via NDRG1. These results indicated a link between KLF4, NDRG1, and DRP1 for the first time, providing new ideas for treating hypoxic pulmonary hypertension.

The prefrontal cortex is differentially involved in implicit and explicit facial emotion processing: An fNIRS study

Despite extensive research, the differential roles of the prefrontal cortex (PFC) in implicit and explicit facial emotion processing remain elusive. Functional near-infrared spectroscopy (fNIRS) is a neuroimaging technique that can measure changes in both oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) concentrations. Currently, how HbO and HbR change during facial emotion processing remains unclear. Here, fNIRS was used to examine and compare PFC activation during implicit and explicit facial emotion processing. Forty young adults performed a facial-matching task that required either emotion discrimination (explicit task) or age discrimination (implicit task), and the activation of their PFCs was measured by fNIRS. Participants attempted the task on two occasions to determine whether their activation patterns were maintained over time. The PFC displayed increases in HbO and/or decreases in HbR during the implicit and explicit facial emotion tasks. Importantly, there were significantly greater changes in PFC HbO during the explicit task, whereas no significant difference in HbR changes between conditions was found. Between sessions, HbO changes were reduced across tasks, but the difference in HbO changes between the implicit and explicit tasks remained unchanged. The test-retest reliability of the behavioral measures was excellent, whereas that of fNIRS measures was mostly poor to fair. Thus, the PFC plays a specific role in recognizing facial expressions, and its differential involvement in implicit and explicit facial emotion processing can be consistently captured at the group level by changes in HbO. This study demonstrates the potential of fNIRS for elucidating the neural mechanisms underlying facial emotion recognition.

The effect of intermittent parathyroid hormone on bone lengthening: current evidence to inform future effective interventions.

Recent studies have demonstrated the positive effects of parathyroid hormone (PTH) on bone healing, and findings support the use of PTH to accelerate bone healing following distraction osteogenesis. The goal of this review was to compile and discuss the mechanisms potentially underlying the effects of PTH on newly formed bone following a bone-lengthening procedure incorporating all relevant evidence in both animal and clinical studies. This review summarized all evidence from in vivo to clinical studies regarding the effects of PTH administration on a bone-lengthening model. In addition, a comprehensive evaluation of what is currently known regarding the potential mechanisms underlying the potential benefits of PTH in bone lengthening was presented. Some controversial findings regarding the optimal dosage and timing of administration of PTH in this model were also discussed. The findings demonstrated that the potential mechanisms associated with the action of PTH on the acceleration of bone regeneration after distraction osteogenesis are involvement in mesenchymal cell proliferation and differentiation, endochondral bone formation, membranous bone formation, and callus remodeling. In the last 20 years, a number of animal and clinical studies have indicated that there is a prospective role for PTH treatment in human bone lengthening as an anabolic agent that accelerates the mineralization and strength of the regenerated bone. Therefore, PTH treatment can be viewed as a potential treatment to increase the amount of new calcified bone and the mechanical strength of the bone in order to shorten the consolidation stage after bone lengthening.

ADAMTS4 Enhances Oligodendrocyte Differentiation and Remyelination by Cleaving NG2 Proteoglycan and Attenuating PDGFRα Signaling.

Although NG2 is known to be selectively expressed in oligodendrocyte precursor cells (OPCs) for many years, its expressional regulation and functional involvement in oligodendrocyte differentiation have remained elusive. Here, we report that the surface-bound NG2 proteoglycan can physically bind to PDGF-AA and enhances PDGF receptor alpha (PDGFRα) activation of downstream signaling. During differentiation stage, NG2 protein is cleaved by A disintegrin and metalloproteinase with thrombospondin motifs type 4 (Adamts4), which is highly upregulated in differentiating OPCs but gradually downregulated in mature myelinating oligodendrocytes. Genetic ablation of Adamts4 gene impedes NG2 proteolysis, leading to elevated PDGFRα signaling but impaired oligodendrocyte differentiation and axonal myelination in both sexes of mice. Moreover, Adamts4 deficiency also lessens myelin repair in adult brain tissue following Lysophosphatidylcholine-induced demyelination. Thus, Adamts4 could be a potential therapeutic target for enhancing oligodendrocyte differentiation and axonal remyelination in demyelinating diseases.SIGNIFICANCE STATEMENT NG2 is selectively expressed in OPCs and downregulated during differentiation stage. To date, the molecular mechanism underlying the progressive removal of NG2 surface proteoglycan in differentiating OPCs has been unknown. In this study, we demonstrate that ADAMTS4 released by differentiating OPCs cleaves surface NG2 proteoglycan, attenuates PDGFRα signaling, and accelerates oligodendrocyte differentiation. In addition, our study also suggests ADAMTS4 as a potential therapeutic target for promoting myelin recovery in demyelinating diseases.

Accurate Bayesian segmentation of thalamic nuclei using diffusion MRI and an improved histological atlas

The human thalamus is a highly connected brain structure, which is key for the control of numerous functions and is involved in several neurological disorders. Recently, neuroimaging studies have increasingly focused on the volume and connectivity of the specific nuclei comprising this structure, rather than looking at the thalamus as a whole. However, accurate identification of cytoarchitectonically designed histological nuclei on standard in vivo structural MRI is hampered by the lack of image contrast that can be used to distinguish nuclei from each other and from surrounding white matter tracts. While diffusion MRI may offer such contrast, it has lower resolution and lacks some boundaries visible in structural imaging. In this work, we present a Bayesian segmentation algorithm for the thalamus. This algorithm combines prior information from a probabilistic atlas with likelihood models for both structural and diffusion MRI, allowing segmentation of 25 thalamic labels per hemisphere informed by both modalities. We present an improved probabilistic atlas, incorporating thalamic nuclei identified from histology and 45 white matter tracts surrounding the thalamus identified in ultra-high gradient strength diffusion imaging. We present a family of likelihood models for diffusion tensor imaging, ensuring compatibility with the vast majority of neuroimaging datasets that include diffusion MRI data. The use of these diffusion likelihood models greatly improves identification of nuclear groups versus segmentation based solely on structural MRI. Dice comparison of 5 manually identifiable groups of nuclei to ground truth segmentations show improvements of up to 10 percentage points. Additionally, our chosen model shows a high degree of reliability, with median test-retest Dice scores above 0.85 for four out of five nuclei groups, whilst also offering improved detection of differential thalamic involvement in Alzheimer’s disease (AUROC 81.98%). The probabilistic atlas and segmentation tool will be made publicly available as part of the neuroimaging package FreeSurfer (https://freesurfer.net/fswiki/ThalamicNucleiDTI).

Variants in PSMB9 and FGR differentially affect Parkinson's disease risk in GBA and LRRK2 mutation carriers

IntroductionRecent studies found an association between Parkinson's disease (PD) and alterations in the innate immune system. However, whether the involvement of this system in two of the known genetic forms of PD, GBA-PD and LRRK2-PD, and in patients who do not carry these mutations is different, is yet to be determined. We aimed to test if genetic variations in the innate immune genes are differentially associated with PD in these subgroups. MethodsInnate immune genes were identified and classified into sub-lists according to Reactome pathways. Whole-genome-sequencing (WGS) was performed on 201 unrelated Ashkenazi-Jewish (AJ) PD patients including 104 GBA-PD, 32 LRRK2-PD, and 65 non-carriers-PD (NC-PD). To identify genes with different burden between these subgroups of PD, gene-based Sequence kernel association optimal unified test (SKAT-O) analysis was performed on innate immune pathways. Candidate variants within the significant genes were further genotyped in a cohort of 1200 unrelated, consecutively recruited, AJ-PD patients, and to evaluate their association with PD-risk their allele frequencies were compared to AJ-non-neuro cases in gnomAD database, in a stratified and un-stratified manner. ResultsSKAT-O analysis showed significantly different burden for PSMB9 (GBA-PD versus NC-PD) and FGR (GBA-PD versus LRRK2-PD). Two candidate variants in PSMB9 showed an association with GBA-PD-risk and NC-PD-risk while one FGR variant showed an association with LRRK2-PD-risk. ConclusionOur data supports differential involvement of innate immunity risk alleles in PD and emphasizes the differences between the GBA- and LRRK2-PD subgroups.

Severe cutaneous drug reactions in children

Severe cutaneous drug reactions also occur in children and range from reactions withblister forming of skin and mucosa to extensive exanthems with altered differential blood count and involvement of internal organs. The first group includes Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), which are considered as one disease entity with different degrees of severity and are also referred to as "epidermal" or "epithelial necrolysis" (EN). The group of drug reactions with primarily systemic alterations is represented by acondition known as drug reaction with eosinophilia and systemic symptoms (DRESS).Although EN is generally considered as adrug reaction, acausative agent can only be identified in about 50% of all pediatric cases. Once aclear diagnosis is established, specific treatment measures should be carried out, whereby discontinuation of the causative agent plays adecisive role in drug-induced cases. In order to be able to identify and discontinue the drug responsible, adetailed medication history must be obtained. Certain antiepileptic drugs, sulfonamides and sulfasalazine are among the most frequent triggers of EN and DRESS in children. Supportive therapy including appropriate topical treatment, pain management and ophthalmological consultations are of utmost importance in EN but ashort-term immunomodulating treatment with cyclosporineA has been shown to be helpful. In contrast, in DRESS middle to long-term systemic treatment with glucocorticosteroids is recommended.

Farm Exposures and Allergic Disease Among Children Living in a Rural Setting

ABSTRACT Objectives The purpose of this study was to examine the association between farm exposures and asthma and allergic disease in children while also highlighting the experiences of non-farm rural children. Methods This was a cross-sectional analysis of data collected from across the province of Saskatchewan, Canada in 2014. Surveys were completed by parents of 2275 rural dwelling children (farm and non-farm) aged 0 to 17 years within 46 rural schools. Questionnaires were distributed through schools for parents to complete. Results Asthma prevalence was 7.6%, of which 29.5% of cases were allergic. After adjustment for potential confounders, home location (farm vs non-farm) and other farm exposures were not associated with asthma and asthma phenotypes. Those who completed farm safety education were more likely to have asthma (11.7% vs. 6.7%; p = .001) compared to children without asthma. In sub-analyses among 6–12-year-old children, boys were more likely to have asthma (non-allergic) and use short-acting beta-agonists compared to girls. Doing farm work in the summer was associated with an increased risk of asthma [adjusted OR (aOR) = 1.71 (1.02–2.88); p = .041]. Doing routine chores with large animals was associated with an increased risk of asthma [aOR = 1.83 (1.07–3.15); p = .027] and allergic asthma [aOR = 2.37 (95%CI = 1.04–5.40); p = .04]. Conclusion The present study showed that the prevalence of asthma and asthma phenotypes were similar between farm and non-farm rural children. There did not appear to be differential involvement in farming activities between those with and without asthma although those with asthma had more training suggesting possible attempts to mitigate harm from farm exposures.

Differential involvement of hippocampal subfields in the relationship between Alzheimer's pathology and memory interference in older adults.

We tested whether Alzheimer's disease (AD) pathology predicts memory deficits in non-demented older adults through its effects on medial temporal lobe (MTL) subregional volume. Thirty-two, non-demented older adults with cerebrospinal fluid (CSF) (amyloid-beta [Aβ]42/Aβ40, phosphorylated tau [p-tau]181, total tau [t-tau]), positron emission tomography (PET; 18F-florbetapir), high-resolution structural magnetic resonance imaging (MRI), and neuropsychological assessment were analyzed. We examined relationships between biomarkers and a highly granular measure of memory consolidation, retroactive interference (RI). Biomarkers of AD pathology were related to RI. Dentate gyrus (DG) and CA3 volume were uniquely associated with RI, whereas CA1 and BA35 volume were related to both RI and overall memory recall. AD pathology was associated with reduced BA35, CA1, and subiculum volume. DG volume and Aβ were independently associated with RI, whereas CA1 volume mediated the relationship between AD pathology and RI. Integrity of distinct hippocampal subfields demonstrate differential relationships with pathology and memory function, indicating specificity in vulnerability and contribution to different memory processes.

Genome-Wide Urea Response in Rice Genotypes Contrasting for Nitrogen Use Efficiency.

Rice is an ideal crop for improvement of nitrogen use efficiency (NUE), especially with urea, its predominant fertilizer. There is a paucity of studies on rice genotypes contrasting for NUE. We compared low urea-responsive transcriptomes of contrasting rice genotypes, namely Nidhi (low NUE) and Panvel1 (high NUE). Transcriptomes of whole plants grown with media containing normal (15 mM) and low urea (1.5 mM) revealed 1497 and 2819 differentially expressed genes (DEGs) in Nidhi and Panvel1, respectively, of which 271 were common. Though 1226 DEGs were genotype-specific in Nidhi and 2548 in Panvel1, there was far higher commonality in underlying processes. High NUE is associated with the urea-responsive regulation of other nutrient transporters, miRNAs, transcription factors (TFs) and better photosynthesis, water use efficiency and post-translational modifications. Many of their genes co-localized to NUE-QTLs on chromosomes 1, 3 and 9. A field evaluation under different doses of urea revealed better agronomic performance including grain yield, transport/uptake efficiencies and NUE of Panvel1. Comparison of our urea-based transcriptomes with our previous nitrate-based transcriptomes revealed many common processes despite large differences in their expression profiles. Our model proposes that differential involvement of transporters and TFs, among others, contributes to better urea uptake, translocation, utilization, flower development and yield for high NUE.

What Do Overrepresented and Underrepresented Groups Tell Us About Risks for Involvement in Islamist Extremism?

On the basis of empirical research on an underrepresented group—Turkish-Dutch youngsters—and an overrepresented group—converts—in Islamist extremist movements, we want to contribute to the debate on what fosters radicalization and resilience. While in both the underrepresented and the overrepresented group there are ample factors recognizable that are commonly identified as contributing to radicalization, Turkish-Dutch youngsters hardly become involved in Islamist extremism, while converts are involved to a larger extent than one might expect on the basis of the number of converts. To shed light on these findings, we will demonstrate how this differential involvement can be understood through the concept of “relational embeddedness”. 1 We will demonstrate how the relational embeddedness of this underrepresented and overrepresented group contributes in various ways to either the lack of susceptibility or the susceptibility to involvement in Islamist extremist groups. We will do this with reference to their sources of identification, their religious socialization, and the availability of legitimate political pathways. In the concluding discussion, we will argue that these insights can contribute to a more nuanced policy approach.

Cerebrospinal Fluid Panel of Synaptic Proteins in Cerebral Amyloid Angiopathy and Alzheimer's Disease.

Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA) share pathogenic pathways related to amyloid-β deposition. Whereas AD is known to affect synaptic function, such an association for CAA remains yet unknown. We therefore aimed to investigate synaptic dysfunction in CAA. Multiple reaction monitoring mass spectrometry was used to quantify cerebrospinal fluid (CSF) concentrations of 15 synaptic proteins in CAA and AD patients, and age- and sex-matched cognitively unimpaired controls. We included 25 patients with CAA, 49 patients with AD, and 25 controls. Only neuronal pentraxin-2 levels were decreased in the CSF of CAA patients compared with controls (p = 0.04). CSF concentrations of 12 other synaptic proteins were all increased in AD compared with CAA or controls (all p≤0.01) and were unchanged between CAA and controls. Synaptic protein concentrations in the subgroup of CAA patients positive for AD biomarkers (CAA/ATN+; n = 6) were similar to AD patients, while levels in CAA/ATN- (n = 19) were comparable with those in controls. A regression model including all synaptic proteins differentiated CAA from AD at high accuracy levels (area under the curve 0.987). In contrast to AD, synaptic CSF biomarkers were found to be largely unchanged in CAA. Moreover, concomitant AD pathology in CAA is associated with abnormal synaptic protein levels. Impaired synaptic function in AD was confirmed in this independent cohort. Our findings support an apparent differential involvement of synaptic dysfunction in CAA and AD and may reflect distinct pathological mechanisms.

Elucidating medial temporal and frontal lobe contributions to approach-avoidance conflict decision-making using functional MRI and the hierarchical drift diffusion model.

The prefrontal cortex (PFC) has long been associated with arbitrating between approach and avoidance in the face of conflicting and uncertain motivational information, but recent work has also highlighted medial temporal lobe (MTL) involvement. It remains unclear, however, how the contributions of these regions differ in their resolution of conflict information and uncertainty. We designed an fMRI paradigm in which participants approached or avoided object pairs that differed by motivational conflict and outcome uncertainty (complete certainty vs. complete uncertainty). Behavioral data and decision-making parameters estimated using the hierarchical drift diffusion model revealed that participants' responding was driven by conflict rather than uncertainty. Our neural data suggest that PFC areas contribute to cognitive control during approach-avoidance conflict by potentially adjusting response caution and the strength of evidence generated towards either choice, with differential involvement of anterior cingulate cortex and dorsolateral prefrontal cortex. The MTL, on the other hand, appears to contribute to evidence generation, with the hippocampus linked to evidence accumulation for stimuli. Although findings within perirhinal cortex were comparatively equivocal, some evidence suggests contributions to perceptual representations, particularly under conditions of threat. Our findings provide evidence that MTL and PFC regions may contribute uniquely to arbitrating approach-avoidance conflict.

The involvement of Th1 cell differentiation in the anti-tumor effect of purified polysaccharide from Sanghuangporus vaninii in colorectal cancer via multi-omics analysis

Sanghuangporus vaninii is a medicinal mushroom, which has been used as a treatment for various diseases; however, the therapeutic potential and mechanism of action of S. vaninii in colorectal cancer (CRC) remain unknown. Herein, human colon adenocarcinoma cells were used to analyze the anti-CRC effects of the purified polysaccharide of S. vaninii (SVP-A-1) in vitro. In SVP-A-1-treated B6/JGpt-Apcem1Cin (Min)/Gpt male (ApcMin/+) mice, 16S rRNA sequencing was performed on cecal feces, metabolites were examined in serum, and LC-MS/MS protein detection was performed in colorectal tumors. Protein changes were further confirmed by various biochemical detection methods. Water-soluble SVP-A-1 with a molecular weight of 22.5 kDa was first obtained. SVP-A-1 prevented gut microbiota dysbiosis related to metabolic pathways of L-arginine biosynthesis, increased L-citrulline levels in the serum of ApcMin/+ mice, mediated L-arginine synthesis, and improved antigen presentation in dendritic cells and activated CD4+ T cells; the resulting Th1 cells released IFN-γ and TNF-α to act on tumor cells and promoted the sensitivity of tumor cells to cytotoxic T lymphocytes. In summary, SVP-A-1 exerted anti-CRC effects and has excellent potential for CRC treatment.