Transparent Carbon Disclosures:depth in Carbon-reporting of Dutch listed and non-listed companies

Climate change is seen as one of the most relevant challenges for the next coming years, politically and economically. The Dutch government has set targets to reduce national carbon emissions according to the commitments made in Paris in 2015. Since companies substantially contribute to the level of carbon emissions, it is necessary to monitor their carbon emissions to see whether they fulfil their commitments. This research shows to what extent companies in the Netherlands (listed, non-listed family owned and a reference group we refer to as non-listed other companies) report their strategies, implementation and performance regarding carbon emissions and reduction. We find, not surprisingly, that on average listed companies are far more transparent than non-listed companies. Non-listed family owned companies are apparently not active or even not willing to be transparent about their carbon policy. However, we do find that several non-listed companies that score high in the Dutch Transparency Benchmark (non-listed other companies) are just as transparent about carbon emissions as AEX-listed companies that must report due to market regulation. Furthermore, we find that most carbon disclosures are still of a mainly qualitative nature. This could imply that firms’ carbon disclosures are at present mostly a means of storytelling rather than a means of thorough analysis on how climate change risk might affect them and how they have to respond to mitigate these financial and societal risks

Lifelong CRF overproduction is associated with altered gene expression and sensitivity of discrete GABAA and mGlu receptor subtypes

RATIONALE: Repeated activation of corticotropin-releasing factor (CRF) receptors is associated with increased anxiety and enhanced stress responsivity, which may be mediated via limbic GABAergic and glutamatergic transmission. OBJECTIVE: The present study investigated molecular and functional alterations in GABA(A) receptor (GABA(A)R) and metabotropic glutamate receptor (mGluR) responsivity in transgenic mice that chronically overexpress CRF. METHODS: CRF(1) receptor, GABA(A)R, and mGluR sensitivity were determined in CRF-overexpressing mice using the stress-induced hyperthermia (SIH) test. In addition, we measured mRNA expression levels of GABA(A)R α subunits and mGluRs in the amygdala and hypothalamus. RESULTS: CRF-overexpressing mice were less sensitive to the anxiolytic effects of the CRF(1) receptor antagonists CP154,526 and DMP695, the GABA(A)R α(3)-selective agonist TP003 (0–3 mg/kg) and the mGluR(2/3) agonist LY379268 (0–10 mg/kg) in the SIH test. The hypothermic effect of the non-selective GABA(A)R agonist diazepam (0–4 mg/kg) and the α(1)-subunit-selective GABA(A)R agonist zolpidem (0–10 mg/kg) was reduced in CRF-overexpressing mice. No genotype differences were found using the GABA(A)R α(5)-subunit preferential compound SH-053-2′F-R-CH(3) and mGluR(5) antagonists MPEP and MTEP. CRF-overexpressing mice showed decreased expression levels of GABA(A)R α(2) subunit and mGluR(3) mRNA levels in the amygdala, whereas these expression levels were increased in the hypothalamus. CRF-overexpressing mice also showed increased hypothalamic mRNA levels of α(1) and α(5) GABA(A)R subunits. CONCLUSIONS: We found that lifelong CRF overproduction is associated with altered gene expression and reduced functional sensitivity of discrete GABA(A) and mGluR receptor subtypes. These findings suggest that sustained over-activation of cerebral CRF receptors may contribute to the development of altered stress-related behavior via modulation of GABAergic and glutamatergic transmission

cDC2 plasticity and acquisition of a DC3-like phenotype mediated by IL-6 and PGE2 in a patient-derived colorectal cancer organoids model

Metastatic colorectal cancer (CRC) is highly resistant to therapy and prone to recur. The tumor-induced local and systemic immunosuppression allows cancer cells to evade immunosurveillance, facilitating their proliferation and dissemination. Dendritic cells (DCs) are required for the detection, processing, and presentation of tumor antigens, and subsequently for the activation of antigen-specific T cells to orchestrate an effective antitumor response. Notably, successful tumors have evolved mechanisms to disrupt and impair DC functions, underlining the key role of tumor-induced DC dysfunction in promoting tumor growth, metastasis initiation, and treatment resistance. Conventional DC type 2 (cDC2) are highly prevalent in tumors and have been shown to present high phenotypic and functional plasticity in response to tumor-released environmental cues. This plasticity reverberates on both the development of antitumor responses and on the efficacy of immunotherapies in cancer patients. Uncovering the processes, mechanisms, and mediators by which CRC shapes and disrupts cDC2 functions is crucial to restoring their full antitumor potential. In this study, we use our recently developed 3D DC-tumor co-culture system to investigate how patient-derived primary and metastatic CRC organoids modulate cDC2 phenotype and function. We first demonstrate that our collagen-based system displays extensive interaction between cDC2 and tumor organoids. Interestingly, we show that tumor-corrupted cDC2 shift toward a CD14+ population with defective expression of maturation markers, an intermediate phenotype positioned between cDC2 and monocytes, and impaired T-cell activating abilities. This phenotype aligns with the newly defined DC3 (CD14(+) CD1c(+) CD163(+)) subset. Remarkably, a comparable population was found to be present in tumor lesions and enriched in the peripheral blood of metastatic CRC patients. Moreover, using EP2 and EP4 receptor antagonists and an anti-IL-6 neutralizing antibody, we determined that the observed phenotype shift is partially mediated by PGE2 and IL-6. Importantly, our system holds promise as a platform for testing therapies aimed at preventing or mitigating tumor-induced DC dysfunction. Overall, our study offers novel and relevant insights into cDC2 (dys)function in CRC that hold relevance for the design of therapeutic approaches

Genetic analysis of morphological traits in a new, versatile, rapid-cycling Brassica rapa recombinant inbred line population

A recombinant inbred line (RIL) population was produced based on a wide cross between the rapid-cycling and self-compatible genotypes L58, a Caixin vegetable type, and R-o-18, a yellow sarson oil type. A linkage map based on 160 F7 lines was constructed using 100 Single nucleotide polymorphisms (SNPs), 130 AFLP®, 27 InDel, and 13 publicly available SSR markers. The map covers a total length of 1150 centiMorgan (cM) with an average resolution of 4.3 cM/marker. To demonstrate the versatility of this new population, 17 traits, related to plant architecture and seed characteristics, were subjected to quantitative trait loci (QTL) analysis. A total of 47 QTLs were detected, each explaining between 6 and 54% of the total phenotypic variance for the concerned trait. The genetic analysis shows that this population is a useful new tool for analyzing genetic variation for interesting traits in B. rapa, and for further exploitation of the recent availability of the B. rapa whole genome sequence for gene cloning and gene function analysis

Crucial factors preceding compulsory psychiatric admission

BACKGROUND: Compulsory admissions have a strong effect on psychiatric patients and represent a deprivation of personal liberty. Although the rate of such admissions is tending to rise in several Western countries, there is little qualitative research on the mental health-care process preceding compulsory admission. The objective of the study was to identify crucial factors in the mental health-care process preceding compulsory admission of adult psychiatric patients. METHODS: This retrospective, qualitative multiple-case study was based on the patient records of patients with severe mental illness, mainly schizophrenia and other psychotic disorders. Twenty two patient records were analyzed. Patients' demographic and clinical characteristics were heterogeneous. All were treated by Flexible Assertive Community Treatment teams (FACT teams) at two mental health institutions in the greater Rotterdam area in the Netherlands and had a compulsory admission in a predefined inclusion period. The data were analyzed according to the Prevention and Recovery System for Monitoring and Analysis (PRISMA) method, assessing acts, events, conditions, and circumstances, failing protective barriers and protective recovery factors. RESULTS: The most important patient factors in the process preceding compulsory admission were psychosis, aggression, lack of insight, care avoidance, and unauthorized reduction or cessation of medication. Neither were health-care professionals as assertive as they could be in managing early signs of relapse and care avoidance of these particular patients. CONCLUSION: The health-care process preceding compulsory admission is complex, being influenced by acts, events, conditions and circumstances, failing barriers, and protective factors. The most crucial factors are patients' lack of insight and cessation of medication, and health-care professionals' lack of assertiveness

Demonstration of Protein-Based Human Identification Using the Hair Shaft Proteome

YesHuman identification from biological material is largely dependent on the ability to characterize genetic polymorphisms in DNA. Unfortunately, DNA can degrade in the environment, sometimes below the level at which it can be amplified by PCR. Protein however is chemically more robust than DNA and can persist for longer periods. Protein also contains genetic variation in the form of single amino acid polymorphisms. These can be used to infer the status of non-synonymous single nucleotide polymorphism alleles. To demonstrate this, we used mass spectrometry-based shotgun proteomics to characterize hair shaft proteins in 66 European-American subjects. A total of 596 single nucleotide polymorphism alleles were correctly imputed in 32 loci from 22 genes of subjects’ DNA and directly validated using Sanger sequencing. Estimates of the probability of resulting individual non-synonymous single nucleotide polymorphism allelic profiles in the European population, using the product rule, resulted in a maximum power of discrimination of 1 in 12,500. Imputed non-synonymous single nucleotide polymorphism profiles from European–American subjects were considerably less frequent in the African population (maximum likelihood ratio = 11,000). The converse was true for hair shafts collected from an additional 10 subjects with African ancestry, where some profiles were more frequent in the African population. Genetically variant peptides were also identified in hair shaft datasets from six archaeological skeletal remains (up to 260 years old). This study demonstrates that quantifiable measures of identity discrimination and biogeographic background can be obtained from detecting genetically variant peptides in hair shaft protein, including hair from bioarchaeological contexts.The Technology Commercialization Innovation Program (Contracts #121668, #132043) of the Utah Governors Office of Commercial Development, the Scholarship Activitie