Studenteninspraak bij Bestuurskunde

In het onderwijsmemorandum van oktober konden de studenten een stuk lezen over de activiteiten die de studentleden in het vakgroepsbestuur hebben opgezet om iets te doen aan de eindeloze stroom organisatorische fouten binnen het onderwijsprogramma. Inmiddels zijn er verdere ontwikkelingen, waar diezelfde leden de studenten op de hoogte van willen houden. Een verslag

Sesamin suppresses activation of microglia and p44/42 MAPK pathway, which confers neuroprotection in rat intracerebral hemorrhage.

Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 μM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH.Thrombin plays important roles in the pathology of intracerebral hemorrhage (ICH). The recruitment of activated microglia, accompanied by thrombin-induced phosphorylation of the mitogen-activated protein kinase (MAPK) family, contributes to ICH-associated neuron loss. Here we investigated the possibility that sesamin, a lignan of sesame seed oil, is a natural candidate as an inhibitor of microglial activation and MAPK pathways under ICH insults. Sesamin (30-100 μM) suppressed thrombin-induced nitric oxide (NO) production by primary-cultured rat microglia via inhibition of inducible NO synthase (iNOS) protein expression, independently of the antioxidative effect. Sesamin selectively inhibited p44/42 MAPK phosphorylation in the MAPK family (p38 and p44/42) involved in iNOS protein expression in primary-cultured rat microglia. An in vivo rat ICH model was prepared by intrastriatal injection of 0.20U collagenase type IV unilaterally. ICH evoked the phosphorylation of p44/42 MAPK, microglial proliferation with morphological change into the activated ameboid form, and neuron loss. The phosphorylation of p44/42 MAPK was inhibited by intracerebroventricular administration of 30-nmol sesamin. Sesamin prevented ICH-induced increase of microglial cells in the perihematomal area. Notably, ramified microglia, the resting morphology, were observed in brain sections of the animals administrated sesamin. Sesamin furthermore achieved neuroprotection in the perihematomal area but not in the hematomal center. These results suggest that sesamin is a promising natural product as a novel therapeutic strategy based on the regulation of microglial activities accompanied by the activated p44/42 MAPK pathway in ICH

A Systematic Mapping Approach of 16q12.2/FTO and BMI in More Than 20,000 African Americans Narrows in on the Underlying Functional Variation: Results from the Population Architecture using Genomics and Epidemiology (PAGE) Study

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3×10-6) had not been highlighted in previous studies. While rs56137030was correlated at r2>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations

Impact of long-term measures of glucose and blood pressure on the retinal microvasculature

Retinopathy and retinal microvascular abnormalities are common in adult populations, yet few long-term predictors have been identified. We therefore examined the association between systolic blood pressure (SBP) and fasting plasma glucose, assessed over 18 years, with retinopathy and retinal vascular caliber in 2,066 Carotid MRI participants, an Atherosclerosis Risk in Communities ancillary study

Ancestral Diversity in Lipoprotein(a) Studies Helps Address Evidence Gaps

INTRODUCTION: The independent and causal cardiovascular disease risk factor lipoprotein(a) (Lp(a)) is elevated in \u3e1.5 billion individuals worldwide, but studies have prioritised European populations. METHODS: Here, we examined how ancestrally diverse studies could clarify Lp(a)\u27s genetic architecture, inform efforts examining application of Lp(a) polygenic risk scores (PRS), enable causal inference and identify unexpected Lp(a) phenotypic effects using data from African (n=25 208), East Asian (n=2895), European (n=362 558), South Asian (n=8192) and Hispanic/Latino (n=8946) populations. RESULTS: Fourteen genome-wide significant loci with numerous population specific signals of large effect were identified that enabled construction of Lp(a) PRS of moderate (R CONCLUSIONS: Our results emphasise the merits of prioritising ancestral diversity when addressing Lp(a) evidence gaps

Exploring the genetic basis of chronic periodontitis: a genome-wide association study

Chronic periodontitis (CP) is a common oral disease that confers substantial systemic inflammatory and microbial burden and is a major cause of tooth loss. Here, we present the results of a genome-wide association study of CP that was carried out in a cohort of 4504 European Americans (EA) participating in the Atherosclerosis Risk in Communities (ARIC) Study (mean age—62 years, moderate CP—43% and severe CP—17%). We detected no genome-wide significant association signals for CP; however, we found suggestive evidence of association (P < 5 × 10−6) for six loci, including NIN, NPY, WNT5A for severe CP and NCR2, EMR1, 10p15 for moderate CP. Three of these loci had concordant effect size and direction in an independent sample of 656 adult EA participants of the Health, Aging, and Body Composition (Health ABC) Study. Meta-analysis pooled estimates were severe CP (n = 958 versus health: n = 1909)—NPY, rs2521634 [G]: odds ratio [OR = 1.49 (95% confidence interval (CI = 1.28–1.73, P = 3.5 × 10−7))]; moderate CP (n = 2293)—NCR2, rs7762544 [G]: OR = 1.40 (95% CI = 1.24–1.59, P = 7.5 × 10−8), EMR1, rs3826782 [A]: OR = 2.01 (95% CI = 1.52–2.65, P = 8.2 × 10−7). Canonical pathway analysis indicated significant enrichment of nervous system signaling, cellular immune response and cytokine signaling pathways. A significant interaction of NUAK1 (rs11112872, interaction P = 2.9 × 10−9) with smoking in ARIC was not replicated in Health ABC, although estimates of heritable variance in severe CP explained by all single nucleotide polymorphisms increased from 18 to 52% with the inclusion of a genome-wide interaction term with smoking. These genome-wide association results provide information on multiple candidate regions and pathways for interrogation in future genetic studies of CP

Coordinated changes in energy intake and expenditure following hypothalamic administration of neuropeptides involved in energy balance

OBJECTIVE: The hypothalamic control of energy balance is regulated by a complex network of neuropeptide-releasing neurons. Whilst the effect of these neuropeptides on individual aspects of energy homeostasis has been studied, the coordinated response of these effects has not been comprehensively investigated. We have simultaneously monitored a number of metabolic parameters following ICV administration of 1nmol and 3nmol of neuropeptides with established roles in the regulation of feeding, activity and metabolism. Ad libitum fed rats received the orexigenic neuropeptides neuropeptide Y (NPY), agouti-related protein (AgRP), melanin-concentrating hormone (MCH) or orexin-A. Overnight food deprived rats received an ICV injection of the anorectic peptides α-MSH, corticotrophin releasing factor (CRF) or neuromedin U (NMU). RESULTS: Our results reveal the temporal sequence of the effects of these neuropeptides on both energy intake and expenditure, highlighting key differences in their function as mediators of energy balance. NPY and AgRP increased feeding and decreased oxygen consumption, with the effects of AgRP being more prolonged. In contrast, orexin-A increased both feeding and oxygen consumption, consistent with an observed increase in activity. The potent anorexigenic effects of CRF were accompanied by a prolonged increase in activity whilst NMU injection resulted in significant but short-lasting inhibition of food intake, ambulatory activity and oxygen consumption. Alpha-MSH injection resulted in significant increases in both ambulatory activity and oxygen consumption, and reduced food intake following administration of 3nmol of the peptide. CONCLUSION: We have for the first time, simultaneously measured several metabolic parameters following hypothalamic administration of a number of neuropeptides within the same experimental system. This work has demonstrated the interrelated effects of these neuropeotides on activity, energy expenditure and food intake thus facilitating comparison between the different hypothalamic systems

Education is associated with lower levels of abdominal obesity in women with a non-agricultural occupation: an interaction study using China's Four Provinces survey.

The prevalence of obesity is increasing rapidly in low- and middle-income countries (LMICs) as their populations become exposed to obesogenic environments. The transition from an agrarian to an industrial and service-based economy results in important lifestyle changes. Yet different socioeconomic groups may experience and respond to these changes differently. Investigating the socioeconomic distribution of obesity in LMICs is key to understanding the causes of obesity but the field is limited by the scarcity of data and a uni-dimensional approach to socioeconomic status (SES). This study splits socioeconomic status into two dimensions to investigate how educated women may have lower levels of obesity in a context where labour market opportunities have shifted away from agriculture to other forms of employment. The Four Provinces Study in China 2008/09 is a household-based community survey of 4,314 people aged ≥60  years (2,465 women). It was used to investigate an interaction between education (none/any) and occupation (agricultural/non-agricultural) on high-risk central obesity defined as a waist circumference ≥80 cm. An interaction term between education and occupation was incorporated in a multivariate logistic regression model, and the estimates adjusted for age, parity, urban/rural residence and health behaviours (smoking, alcohol, meat and fruit & vegetable consumption). Complete case analyses were undertaken and results confirmed using multiple imputation to impute missing data. An interaction between occupation and education was present (P = 0.02). In the group with no education, the odds of central obesity in the sedentary occupation group were more than double those of the agricultural occupation group even after taking age group and parity into account (OR; 95%CI: 2.21; 1.52, 3.21), while in the group with any education there was no evidence of such a relationship (OR; 95%CI: 1.25; 0.92, 1.70). Health behaviours appeared to account for some of the association. These findings suggest that education may have a protective role in women against the higher odds of obesity associated with occupational shifts in middle-income countries, and that investment in women's education may present an important long term investment in obesity prevention. Further research could elucidate the mechanisms behind this association