Depression pandemic and cardiovascular risk in the COVID-19 era and long COVID syndrome: gender makes a difference

The ongoing COVID-19 pandemic highlighted a significant interplay between cardiovascular disease (CVD), COVID-19 related inflammatory status, and depression. Cardiovascular (CV) injury is responsible for a substantial percentage of COVID-19 deaths while COVID-19 social restrictions emerged as a non-negligible risk factor for CVD as well as a variety of mental health issues, and in particular, depression. Inflammation seems to be a shared condition between these two disorders. Gender represents a potential modifying factor both in CVD and depression, as well as in COVID-19 short- and long-term outcomes, particularly in cases involving long-term COVID complications. Results from emerging studies indicate that COVID-19 pandemic affected male and female populations in different ways. Women seem to experience less severe short-term complications but suffer worse long-term COVID complications, including depression, reduced physical activity, and deteriorating lifestyle habits, all of which may impact CV risk. Here, we summarize the current state of knowledge about the interplay between COVID-19, depression, and CV risk in women

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Background: non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results: we performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. Conclusions: the primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

\u3cem\u3eN\u3c/em\u3e-Acylethanolamines as Novel Alcohol Dehydrogenase 3 Substrates

N-Acylethanolamines (NAEs) are a class of fatty acid amides that act as important mammalian signaling molecules. N-Arachidonoylethanolamine is the best-studied representative and is one of the endogenous ligands for endocannabinoid receptors. NAEs play a role in the regulation of appetite, act as anti-inflammatory and analgesic agents, and are thought to have a neuroprotective function as well. They have been proposed to also serve as precursors to N-acylglycines (NAGs). N-Acylglycinals are likely to be intermediates between the NAEs and the NAGs. The sequential actions of a putative fatty alcohol dehydrogenase and a putative fatty aldehyde dehydrogenase are thought to affect the NAD+-dependent oxidation of the NAEs to the NAGs. NAGs, in turn, serve as precursor in the biosynthesis of primary fatty acid amides (PFAMs), another class of mammalian regulatory molecules. Alcohol dehydrogenase 3 (ADH3), an enzyme known to oxidize mid- and long-chain alcohols to aldehydes, was evaluated for its potential in oxidation of NAEs to N-acylglycinals. In order to evaluate the possibility of ADH3 involvement in NAE metabolism, variable chain length NAEs were synthesized and evaluated as substrates for bovine liver ADH3. NAEs were oxidized by ADH3 in the presence of NAD+, yielding the corresponding N-acylglycinals. VMax/KM values for assayed NAEs were low relative to cinnamyl alcohol, one of the preferred substrates for ADH3. Our data suggest that the ADH-mediated oxidation of NAEs could occur in vivo, but that ADH3 is unlikely to be the in vivo catalyst

\u3cem\u3eN\u3c/em\u3e-Acylethanolamines as Novel Alcohol Dehydrogenase 3 Substrates

N-Acylethanolamines (NAEs) are a class of fatty acid amides that act as important mammalian signaling molecules. N-Arachidonoylethanolamine is the best-studied representative and is one of the endogenous ligands for endocannabinoid receptors. NAEs play a role in the regulation of appetite, act as anti-inflammatory and analgesic agents, and are thought to have a neuroprotective function as well. They have been proposed to also serve as precursors to N-acylglycines (NAGs). N-Acylglycinals are likely to be intermediates between the NAEs and the NAGs. The sequential actions of a putative fatty alcohol dehydrogenase and a putative fatty aldehyde dehydrogenase are thought to affect the NAD+-dependent oxidation of the NAEs to the NAGs. NAGs, in turn, serve as precursor in the biosynthesis of primary fatty acid amides (PFAMs), another class of mammalian regulatory molecules. Alcohol dehydrogenase 3 (ADH3), an enzyme known to oxidize mid- and long-chain alcohols to aldehydes, was evaluated for its potential in oxidation of NAEs to N-acylglycinals. In order to evaluate the possibility of ADH3 involvement in NAE metabolism, variable chain length NAEs were synthesized and evaluated as substrates for bovine liver ADH3. NAEs were oxidized by ADH3 in the presence of NAD+, yielding the corresponding N-acylglycinals. VMax/KM values for assayed NAEs were low relative to cinnamyl alcohol, one of the preferred substrates for ADH3. Our data suggest that the ADH-mediated oxidation of NAEs could occur in vivo, but that ADH3 is unlikely to be the in vivo catalyst

Low carbon stations for low carbon cities – Final report 2015

1. svensk text Våra stationssamhällen är viktiga för städers och regioners utveckling. En utveckling av dessa samhällen kan möjliggöra en transportsnål samhällsplanering, hållbar ekonomisk utveckling och en attraktiv region. Att förtäta i stationsnära lägen är en gemensam utmaning för många aktörer och intressenter. Mistra Urban Futures driver tillsammans med en rad partners, även Trafikverket, ett projekt om urbana stationssamhällen. Projektet vill öka kunskapen om det komplexa i stationsnära planering och skapa förutsättningar för utveckling av stationssamhällen. Projektet fokuserar på att vitalisera och stötta planeringsprocesser i kommuner för att kunna bygga transporteffektiva region med attraktiva och täta stationssamhällen. Flera delprojekt genomförs för att öka kunskapen och Low carbon stations for low carbon cities är ett delprojekt. Mistra Urban Futures anser att utformningen av kollektivtrafiknoder är en viktig parameter för att öka resandet med kollektivtrafiken och minska utsläppen av koldioxid. Utformningen av stationslägen är en globalt viktig fråga och detta projekt kan tillföra viktig kunskap till plattformarna inom Mistra Urban Futures. Trafikverket har finansierat det europeiska forskarteamet YDF för arbetet med "Low carbon stations for low carbon cities" - en forskning om stationsområden och hur man genom en effektivare utformning och planering av flöden för resor och transporter kan minska koldioxidutsläppen. Syftet med forskningen har varit att få fram generella rekommendationer som kan användas vid utformning av stationsområden och dess flöden. Med syfte att få underlag för en generaliserbar kunskap med rekommendationer som kan användas i alla länder, har YDF undersökt och jämfört stationsområdens utformning, funktioner och möjligheter i flera världsdelars städer. I Sverige har YDF undersökt stationsområdena i Stockholm, Malmö och Göteborg. Projektets ena rapportdel innehåller övergripande frågeställningar om energieffektivitet kopplat till resor, transporter och design för hållbarhet i storstadsregioner utifrån ett stationsperspektiv. Projektets andra rapportdel innehåller konkreta råd och rekommendationer om metoder och utformning med användbar kunskap som efterfrågas allt mer. Anne Leemans, generalsekreterare i stiftelsen YDF: ” Som medborgare och formgivare känner vi ansvar att göra vad vi kan för att mildra klimatförändringarna. Vi började forska ur resenärsperspektivet och kopplingen mellan upplevd säkerhet och design av urbana transporter och utvecklade en metod för att förbättra den upplevda tryggheten i och omkring stationerna. Det har visat sig vara viktigt att inte bara öka antalet passagerare och användare av stationen men också för att öka detaljhandeln på stationen. Hur kan vi påverka kollektivtrafikens attraktion hos resenärerna? Hur kan vi öka tilliten för kollektivtrafiken? Nästa fråga var, med tanke på behovet av tillgänglighet, lokalisering och minskad klimatpåverkan, hur kan vi bidra till en bättre integrering av stationer i stadens urbana struktur i olika delar av världen.” 2. English The future role of station communities is crucial for urban and regional development. A development of these communities can enable a transport-efficient urban planning, a sustainable economic development and an attractive region. Densifying station neighborhoods is a common challenge for many actors and stakeholders. Mistra Urban Futures are therefore along with several partners, Swedish Transport Administration is one of them, in the process of developing a project about urban station communities. The project will increase knowledge about the complexity in planning station near locations and create conditions for development of station communities. The project focuses on revitalizing and supporting municipalities regular planning processes to stimulate the building of an efficient transport region with attractive and dense station communities. Mistra Urban Futures think that the design of public transport nodes is an important parameter to increase travel by public transport and reduce emissions of carbon dioxide. The design of the station locations is a globally important issue and the project can bring important knowledge to the platforms in Mistra Urban Futures. The Swedish Transport Administration has funded the European research team YDF for the work of the "Low Carbon station for low carbon cities" - a research of station areas and how, through effective design and planning of flows for travel and transport can reduce carbon emissions. Purpose of the research has been to develop general recommendations that can be used in the design of the station areas and its flows. To get a basis for a generalizable knowledge with recommendations that can be used in all countries, has YDF examined and compared station areas design, features and capabilities in several continents cities. In Sweden has the station areas in Stockholm, Malmö and Gothenburg been examined. The first part of the project’s report contains general questions about the energy efficiency linked to the travel, transportation and design for sustainability in metropolitan regions from a station perspective. The project's second part of the report contains advice and recommendations on methods, the design of useful knowledge that are increasingly in demand. Anne Leemans , Secretary General of the Foundation YDF: “As citizens and design professionals we moreover feel we have an obligation to undertake what is within our power and capacity to help mitigate climate change. We started doing research from the perspective of passengers on the link between perceived security and design of urban public transport stations and developed a methodology to improve perceived security in and around stations. It has proved to be important not only to increase the number of passengers and users of the station but also to boost the turn-over of retailers in the station. How can we positively influence the attraction of public transport to passenger? How can we make sure more people trust public transport? The next question was, considering the need for accessible mobility is location and climate independant, how can we contribute to a better integration of stations in the urban tissue both in the global South and North.”Mistra Urban Future

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Background: non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results: we performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. Conclusions: the primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Background: non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results: we performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients' overall survival. Conclusions: the primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

N-BLR, a primate-specific non-coding transcript leads to colorectal cancer invasion and migration

Abstract Background Non-coding RNAs have been drawing increasing attention in recent years as functional data suggest that they play important roles in key cellular processes. N-BLR is a primate-specific long non-coding RNA that modulates the epithelial-to-mesenchymal transition, facilitates cell migration, and increases colorectal cancer invasion. Results We performed multivariate analyses of data from two independent cohorts of colorectal cancer patients and show that the abundance of N-BLR is associated with tumor stage, invasion potential, and overall patient survival. Through in vitro and in vivo experiments we found that N-BLR facilitates migration primarily via crosstalk with E-cadherin and ZEB1. We showed that this crosstalk is mediated by a pyknon, a short ~20 nucleotide-long DNA motif contained in the N-BLR transcript and is targeted by members of the miR-200 family. In light of these findings, we used a microarray to investigate the expression patterns of other pyknon-containing genomic loci. We found multiple such loci that are differentially transcribed between healthy and diseased tissues in colorectal cancer and chronic lymphocytic leukemia. Moreover, we identified several new loci whose expression correlates with the colorectal cancer patients’ overall survival. Conclusions The primate-specific N-BLR is a novel molecular contributor to the complex mechanisms that underlie metastasis in colorectal cancer and a potential novel biomarker for this disease. The presence of a functional pyknon within N-BLR and the related finding that many more pyknon-containing genomic loci in the human genome exhibit tissue-specific and disease-specific expression suggests the possibility of an alternative class of biomarkers and therapeutic targets that are primate-specific

Sex differences in oncogenic mutational processes

Funder: Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada (NSERC Canadian Network for Research and Innovation in Machining Technology); doi: https://doi.org/10.13039/501100002790Funder: Genome Canada (Génome Canada); doi: https://doi.org/10.13039/100008762Funder: Canada Foundation for Innovation (Fondation canadienne pour l'innovation); doi: https://doi.org/10.13039/501100000196Funder: Terry Fox Research Institute (Institut de Recherche Terry Fox); doi: https://doi.org/10.13039/501100004376Abstract: Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research