FOXC2 Is a Winged Helix Gene that Counteracts Obesity, Hypertriglyceridemia, and Diet-Induced Insulin Resistance

AbstractObesity, hyperlipidemia, and insulin resistance are common forerunners of type 2 diabetes mellitus. We have identified the human winged helix/forkhead transcription factor gene FOXC2 as a key regulator of adipocyte metabolism. Increased FOXC2 expression, in adipocytes, has a pleiotropic effect on gene expression, which leads to a lean and insulin sensitive phenotype. FOXC2 affects adipocyte metabolism by increasing the sensitivity of the β-adrenergic-cAMP-protein kinase A (PKA) signaling pathway through alteration of adipocyte PKA holoenzyme composition. Increased FOXC2 levels, induced by high fat diet, seem to counteract most of the symptoms associated with obesity, including hypertriglyceridemia and diet-induced insulin resistance—a likely consequence hereof would be protection against type 2 diabetes

Äidin tyypin 1 diabeteksen vaikutus sikiön ja vastasyntyneen terveyteen

Vertaisarvioitu. English summary.Tyypin 1 diabetesta sairastavan naisen raskauteen liittyy merkittävästi suurentunut obstetristen komplikaatioiden ja vastasyntyneen hoidontarpeen riski. Viidesosa tyypin 1 diabetesta sairastavien äitien lapsista joutuu vastasyntyneiden teho-osastolle ja joka toinen lastenosastolle hoitoon synnytyksen jälkeen. Tavallisimpia ongelmia ovat hypoglykemia, makrosomia ja siihen liittyvät synnytysvauriot, vastasyntyneen hengitysongelmat, hyperbilirubinemia ja ennenaikaisuus. Tyypin 1 diabetesta sairastavan naisen raskaus vaatii huolellista suunnittelua ja diabeteksen hoidon optimointia ennen raskautta sekä tiivistä moniammatillista seurantaa raskausaikana. Uudet kansainväliset hoitosuositukset korostavat glukoosipitoisuuden vaihtelun vähentämisen merkitystä. Raskauden suunnittelussa ja raskausajan hoitotavoitteena tuleekin olla riittävä aika glukoositavoitteessa (time in range, TIR). Jatkuvan glukoosiseurannan avulla voidaan vähentää äidin glukoosipitoisuuden vaihtelua ja vastasyntyneen ongelmia.Peer reviewe

Foderproduktion och metanbildning i våmmen utgör 85-90 % av mjölkens klimatpåverkan

Klimatpåverkan från mjölkproduktionen har varit i fokus de senaste åren, inte minst p g a djurens utsläpp av metan. Mjölkens klimatpåverkan består dock inte enbart av metan från foderomvandling i våmmen. Även foderproduktionen står för en betydande andel av växthusgaserna medan t ex transporter och gårdens elförbrukning utgör små andelar

IRS1-Independent Defects Define Major Nodes of Insulin Resistance

SummaryInsulin resistance is a common disorder caused by a wide variety of physiological insults, some of which include poor diet, inflammation, anti-inflammatory steroids, hyperinsulinemia, and dyslipidemia. The common link between these diverse insults and insulin resistance is widely considered to involve impaired insulin signaling, particularly at the level of the insulin receptor substrate (IRS). To test this model, we utilized a heterologous system involving the platelet-derived growth factor (PDGF) pathway that recapitulates many aspects of insulin action independently of IRS. We comprehensively analyzed six models of insulin resistance in three experimental systems and consistently observed defects in both insulin and PDGF action despite a range of insult-specific defects within the IRS-Akt nexus. These findings indicate that while insulin resistance is associated with multiple deficiencies, the most deleterious defects and the origin of insulin resistance occur independently of IRS

Focal brain trauma in the cryogenic lesion model in mice

The method to induce unilateral cryogenic lesions was first described in 1958 by Klatzo. We describe here an adaptation of this model that allows reliable measurement of lesion volume and vasogenic edema by 2, 3, 5-triphenyltetrazolium chloride-staining and Evans blue extravasation in mice. A copper or aluminium cylinder with a tip diameter of 2.5 mm is cooled with liquid nitrogen and placed on the exposed skull bone over the parietal cortex (coordinates from bregma: 1.5 mm posterior, 1.5 mm lateral). The tip diameter and the contact time between the tip and the parietal skull determine the extent of cryolesion. Due to an early damage of the blood brain barrier, the cryogenic cortical injury is characterized by vasogenic edema, marked brain swelling, and inflammation. The lesion grows during the first 24 hours, a process involving complex interactions between endothelial cells, immune cells, cerebral blood flow, and the intracranial pressure. These contribute substantially to the damage from the initial injury. The major advantage of the cryogenic lesion model is the circumscribed and highly reproducible lesion size and location

Large-scale long-term passive-acoustic monitoring reveals spatio-temporal activity patterns of boreal bats

The distribution ranges and spatio-temporal patterns in the occurrence and activity of boreal bats are yet largely unknown due to their cryptic lifestyle and lack of suitable and efficient study methods. We approached the issue by establishing a permanent passive-acoustic sampling setup spanning the area of Finland to gain an understanding on how latitude affects bat species composition and activity patterns in northern Europe. The recorded bat calls were semi-automatically identified for three target taxa; Myotis spp., Eptesicus nilssonii or Pipistrellus nathusii and the seasonal activity patterns were modeled for each taxa across the seven sampling years (2015-2021). We found an increase in activity since 2015 for E. nilssonii and Myotis spp. For E. nilssonii and Myotis spp. we found significant latitude -dependent seasonal activity patterns, where seasonal variation in patterns appeared stronger in the north. Over the years, activity of P. nathusii increased during activity peak in June and late season but decreased in mid season. We found the passive-acoustic monitoring network to be an effective and cost-efficient method for gathering bat activity data to analyze spatio-temporal patterns. Long-term data on the composition and dynamics of bat communities facilitates better estimates of abundances and population trend directions for conservation purposes and predicting the effects of climate change

Monitoring of ticks and tick-borne pathogens through a nationwide research station network in Finland

In 2015 a long-term, nationwide tick and tick-borne pathogen (TBP) monitoring project was started by the Finnish Tick Project and the Finnish Research Station network (RESTAT), with the goal of producing temporally and geographically extensive data regarding exophilic ticks in Finland. In the current study, we present results from the first four years of this collaboration. Ticks were collected by cloth dragging from 11 research stations across Finland in May September 2015-2018 (2012-2018 in Seili). Collected ticks were screened for twelve different pathogens by qPCR: Borrelia afzelii, Borrelia garinii, Borrelia valaisiana, Borrelia burgdorferi sensu stricto, Borrelia miyamotoi, Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, Francisella tularensis, Bartonella spp. and tick-borne encephalitis virus (TBEV). Altogether 15 067 Ixodes ricinus and 46 Ixodes persulcatus were collected during 68 km of dragging. Field collections revealed different seasonal activity patterns for the two species. The activity of I. persulcatus adults (only one nymph detected) was unimodal, with activity only in May July, whereas Ixodes ricinus was active from May to September, with activity peaks in September (nymphs) or July August (adults). Overall, tick densities were higher during the latter years of the study. Borrelia burgdorferi sensu lato were the most common pathogens detected, with 48.9 +/- 8.4% (95% Cl) of adults and 25.3 +/- 4.4% of nymphs carrying the bacteria. No samples positive for F. tularensis, Bartonella or TBEV were detected. This collaboration project involving the extensive Finnish Research Station network has ensured enduring and spatially extensive, long-term tick data collection to the foreseeable future.Peer reviewe

Whole blood co-expression modules associate with metabolic traits and type 2 diabetes : an IMI-DIRECT study

Background The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D. Methods Clusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts. Results We identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling. Conclusions Our results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.Peer reviewe

Monitoring of ticks and tick-borne pathogens through a nationwide research station network in Finland

In 2015 a long-term, nationwide tick and tick-borne pathogen (TBP) monitoring project was started by the Finnish Tick Project and the Finnish Research Station network (RESTAT), with the goal of producing temporally and geographically extensive data regarding exophilic ticks in Finland. In the current study, we present results from the first four years of this collaboration. Ticks were collected by cloth dragging from 11 research stations across Finland in May–September 2015–2018 (2012–2018 in Seili). Collected ticks were screened for twelve different pathogens by qPCR: Borrelia afzelii, Borrelia garinii, Borrelia valaisiana, Borrelia burgdorferi sensu stricto, Borrelia miyamotoi, Babesia spp., Anaplasma phagocytophilum, Rickettsia spp., Candidatus Neoehrlichia mikurensis, Francisella tularensis, Bartonella spp. and tick-borne encephalitis virus (TBEV). Altogether 15 067 Ixodes ricinus and 46 Ixodes persulcatus were collected during 68 km of dragging. Field collections revealed different seasonal activity patterns for the two species. The activity of I. persulcatus adults (only one nymph detected) was unimodal, with activity only in May–July, whereas Ixodes ricinus was active from May to September, with activity peaks in September (nymphs) or July–August (adults). Overall, tick densities were higher during the latter years of the study. Borrelia burgdorferi sensu lato were the most common pathogens detected, with 48.9 ± 8.4% (95% Cl) of adults and 25.3 ± 4.4% of nymphs carrying the bacteria. No samples positive for F. tularensis, Bartonella or TBEV were detected. This collaboration project involving the extensive Finnish Research Station network has ensured enduring and spatially extensive, long-term tick data collection to the foreseeable future