Regional changes in parvalbumin and calbindin expression in fear memory circuits of the developing mouse brain

Uttrykt i nevroner og vidt distribuert i den voksne musehjernen finner vi kalsiumbindende proteiner. Gjennom utvikling bidrar kalsiumbindende proteiner som parvalbumin og calbindin til modningen av nevrale nettverk som ligger til grunn for en rekke funksjoner, inkludert fryktminneprosesser. Tidligere forskningsfunn konkluderte med at et redusert nivå av disse bindende proteinene kan føre til nevrodegenerative sykdommer og videre være involvert i nevroutviklingsforstyrrelser som angst. Ettersom de fleste studier kun fokuserer på en eller få hjerneregioner er informasjon om antall og tetthetsfordeling av disse kalsiumbindende proteinene i den utviklende musehjernen fragmentert. For å gi en mer omfattende oversikt over mengden og fordeling av kalsiumbindende proteiner i musehjernen, har vi laget en betydelig samling av mer enn 2500 mikroskopiske bilder. Disse bildene viser utviklingsmønsteret til parvalbumin og calbindin positive nevroner, fra musehjerner i alderen 9, 14, 21 og 35 dager. Dette prosjektet gir en analyse fokusert på nettverket som er assosiert med fryktminne, bestående av prelimbisk område, infralimbisk område og basolateral amygdala. Resultatene viser økt nivå av parvalbumin positive nevroner gjennom utvikling mens calbindin nivåer synker. Den største forskjellen ble sett i basolateral amygdala, som indikerer at disse kalsiumbindende proteinene spiller en avgjørende rolle i fryktminneprosesser under utvikling. All data innhentet i dette prosjektet deles offentlig gjennom forskningsinfrastrukturen EBRAINS, som gjør det mulig for forskere å undersøke videre regionale endringer i hjernens arkitektur gjennom utvikling.Calcium-binding proteins expressed in neurons are widely distributed across the adult mouse brain. Through development, calcium-binding proteins such as parvalbumin and calbindin contribute to the maturation of neural networks underlying a range of functions such as fear memory processes. Previous research findings concluded that a decreased level of these binding proteins may result in neurodegeneration and further be involved in neurodevelopmental disorders such as anxiety. Information on the number and density distribution of these binding proteins in the developing mice brain are fragmented, as most studies focus only on one or few brain regions. To provide a more comprehensive overview of the amount and spatial distribution of calcium-binding proteins in the mouse brain, we have created a comprehensive collection of more than 2500 microscopic images. These images illustrate the developmental pattern of parvalbumin and calbindin positive neurons, sampled from the brains of mice aged 9, 14, 21, and 35 days. To demonstrate how this material can be used, the present project provides an analysis focused on areas associated with fear memory networks including prelimbic area, infralimbic area and basolateral amygdala. Our results indicate that parvalbumin levels increase through development while calbindin levels decrease. The largest difference was seen in basolateral amygdala indicating that these binding proteins play a crucial role in fear memory processes during development. All data resulting from this project are publicly shared through the EBRAINS research infrastructure, allowing researchers to further investigate regional changes in brain architecture through development across the entire brain

Global governance approaches to addressing illegal logging: Uptake and lessons learned

One of the most challenging tasks facing development agencies, trade ministries, environmental groups, social activists and forest-focused business interests seeking to ameliorate illegal logging and related timber trade is to identify and nurture promising global governance interventions capable of helping improve compliance to governmental policies and laws at national, subnational and local levels. This question is especially acute for developing countries constrained by capacity challenges and “weak states” (Risse, 2011). This chapter seeks to shed light on this task by asking four related questions: How do we understand the emergence of illegal logging as a matter of global interest? What are the types of global interventions designed to improve domestic legal compliance? How have individual states responded to these global efforts? What are the prospects for future impacts and evolution? We proceed in the following steps. Following this introduction, step two reviews how the problem of “illegal logging” emerged on the international agenda. Step three reviews leading policy interventions that resulted from this policy framing. Step four reviews developments in selected countries/regions around the world according to their place on the global forest products supply chain: consumers (United States, Europe and Australia); middle of supply chain manufacturers (China and South Korea) and producers (Russia; Indonesia; Brazil and Peru; Ghana, Cameroon and the Republic of Congo). We conclude by reflecting on key trends that emerge from this review relevant for understanding the conditions through which legality might make a difference in addressing critical challenges

CD24 Is Not Required for Tumor Initiation and Growth in Murine Breast and Prostate Cancer Models

CD24 is a small, heavily glycosylated, GPI-linked membrane protein, whose expression has been associated with the tumorigenesis and progression of several types of cancer. Here, we studied the expression of CD24 in tumors of MMTV-PyMT, Apc1572/T+ and TRAMP genetic mouse models that spontaneously develop mammary or prostate carcinoma, respectively. We found that CD24 is expressed during tumor development in all three models. In MMTV-PyMT and Apc1572T/+ breast tumors, CD24 was strongly but heterogeneously expressed during early tumorigenesis, but decreased in more advanced stages, and accordingly was increased in poorly differentiated lesions compared with well differentiated lesions. In prostate tumors developing in TRAMP mice, CD24 expression was strong within hyperplastic lesions in comparison with non-hyperplastic regions, and heterogeneous CD24 expression was maintained in advanced prostate carcinomas. To investigate whether CD24 plays a functional role in tumorigenesis in these models, we crossed CD24 deficient mice with MMTV-PyMT, Apc1572T/+ and TRAMP mice, and assessed the influence of CD24 deficiency on tumor onset and tumor burden. We found that mice negative or positive for CD24 did not significantly differ in terms of tumor initiation and burden in the genetic tumor models tested, with the exception of Apc1572T/+ mice, in which lack of CD24 reduced the mammary tumor burden slightly but significantly. Together, our data suggest that while CD24 is distinctively expressed during the early development of murine mammary and prostate tumors, it is not essential for the formation of tumors developing in MMTV-PyMT, Apc1572T/+ and TRAMP mice

National laboratory-based surveillance system for antimicrobial resistance: a successful tool to support the control of antimicrobial resistance in the Netherlands

An important cornerstone in the control of antimicrobial resistance (AMR) is a well-designed quantitative system for the surveillance of spread and temporal trends in AMR. Since 2008, the Dutch national AMR surveillance system, based on routine data from medical microbiological laboratories (MMLs), has developed into a successful tool to support the control of AMR in the Netherlands. It provides background information for policy making in public health and healthcare services, supports development of empirical antibiotic therapy guidelines and facilitates in-depth research. In addition, participation of the MMLs in the national AMR surveillance network has contributed to sharing of knowledge and quality improvement. A future improvement will be the implementation of a new semantic standard together with standardised data transfer, which will reduce errors in data handling and enable a more real-time surveillance. Furthermore, the

Outcome of a ‘step-up approach’ for recurrent cholangitis in patients with a non-stenotic hepaticojejunostomy after hepato-pancreato-biliary surgery: single center series

Background: Recurrent non-stenotic cholangitis (NSC) is a challenging and poorly understood complication of a surgical hepaticojejunostomy (HJ). Optimal treatment remains unclear. Methods: A retrospective single center series including patients with recurrent cholangitis with a non-stenotic HJ after hepato-pancreato-biliary surgery was conducted (2015–2022). Primary outcome was resolution of NSC (i.e. free of NSC during six months). Secondary outcomes included reduction of NSC monthly episode frequency and secondary sclerosing cholangitis. Results: Overall, 50 of 1179 (4.2%) patients with HJ developed NSC. Treatment included a ‘step-up approach’ with short-course antibiotics (n = 50, 100 %), prolonged antibiotics (n = 26, 52%), and revisional surgery (n = 7, 14 %). Resolution of NSC was achieved in 15 patients (30%) and reduction of NSC frequency in an additional 21 patients (42%). Concomitant ursodeoxycholic acid use and discontinuation of proton pump inhibitors was the only predictor for resolution (OR 4.229, p = 0.035). Secondary sclerosing cholangitis occurred in 12 patients (24%) and was associated with the number of NSC episodes (OR 1.2, p = 0.050). Conclusion: A ‘step-up approach’ to recurrent NSC after HJ resulted in 30 % resolution and further 42 % reduced frequency of NSC although still a quarter of patients developed secondary sclerosing cholangitis. Future prospective studies should assess whether a protocolized approach could improve outcomes

Rapid assessment of regional SARS-CoV-2 community transmission through a convenience sample of healthcare workers, the Netherlands, March 2020

To rapidly assess possible community transmission in Noord-Brabant, the Netherlands, healthcare workers (HCW) with mild respiratory complaints and without epidemiological link (contact with confirmed case or visited areas with active

Virulence Potential and Genomic Mapping of the Worldwide Clone Escherichia coli ST131

Recently, the worldwide propagation of clonal CTX-M-15-producing Escherichia coli isolates, namely ST131 and O25b:H4, has been reported. Like the majority of extra-intestinal pathogenic E. coli isolates, the pandemic clone ST131 belongs to phylogenetic group B2, and has recently been shown to be highly virulent in a mouse model, even though it lacks several genes encoding key virulence factors (Pap, Cnf1 and HlyA). Using two animal models, Caenorhabditis elegans and zebrafish embryos, we assessed the virulence of three E. coli ST131 strains (2 CTX-M-15- producing urine and 1 non-ESBL-producing faecal isolate), comparing them with five non-ST131 B2 and a group A uropathogenic E. coli (UPEC). In C. elegans, the three ST131 strains showed intermediate virulence between the non virulent group A isolate and the virulent non-ST131 B2 strains. In zebrafish, the CTX-M-15-producing ST131 UPEC isolates were also less virulent than the non-ST131 B2 strains, suggesting that the production of CTX-M-15 is not correlated with enhanced virulence. Amongst the non-ST131 B2 group isolates, variation in pathogenic potential in zebrafish embryos was observed ranging from intermediate to highly virulent. Interestingly, the ST131 strains were equally persistent in surviving embryos as the non-ST131-group B2 strains, suggesting similar mechanisms may account for development of persistent infection. Optical maps of the genome of the ST131 strains were compared with those of 24 reference E. coli strains. Although small differences were seen within the ST131 strains, the tree built on the optical maps showed that these strains belonged to a specific cluster (86% similarity) with only 45% similarity with the other group B2 strains and 25% with strains of group A and D. Thus, the ST131 clone has a genetic composition that differs from other group B2 strains, and appears to be less virulent than previously suspected