The effect of ambient temperature on the gut microbiota diversity and composition of pied flycatcher (Ficedula hypoleuca) nestlings

Vertebrate guts harbor a diverse community of microbes, which have significant effects on their host’s body functions. Multiple external and internal factors influence the composition of gut microbiota, but the role of ambient temperature in shaping microbial assemblages is still largely unknown. To shed new light on this topic I explored whether temperature drop changes the diversity and composition of gut microbiota of pied flycatcher (Ficedula hypoleuca) nestlings. In addition to my main interest, temperature effects, I also investigated the role of age, the rearing environment, and genetic background in shaping gut microbiota. The role of environment and genetics was surveyed by conducting a partial cross-fostering experiment for 2 days old nestlings. To examine the temperature effects, the experimental cooling of nest boxes was initiated when nestlings were 7 days old and finished when nestlings were 13 days old. The cloacal swab samples were collected before and after the treatment, and the microbiota was surveyed using 16S rRNA sequencing. The cooling experiment did not influence the diversity or composition of nestlings’ gut microbiota and neither did age, even though the relative abundance of Firmicutes increased with age. The rearing environment explained slightly more the variation in gut microbiota than the genetic background. The lack of effect of the cooling treatment on the gut microbiota diversity and composition might be explained by only a minor change in temperature or quite short cooling period. In addition, uncontrolled factors, such as diet, might override the effects of temperature drop

Neutrophil gelatinase-associated lipocalin in kidney and liver transplantation

Expanding the criteria for deceased organ donors increases the risk of delayed graft function (DGF) complicating kidney transplant outcome. Liver transplant recipients are at an increased risk for kidney injury both before and after transplantation and renal dysfunction strongly associates with morbidity and mortality. Identifying kidney injury early is crucial in achieving favorable outcome after transplantation. However, there are currently no reliable methods for predicting kidney damage in transplant patients. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel marker for acute kidney injury. The aim of the study was thus to test whether kidney donor and recipient urine and serum NGAL could predict DGF and prolonged DGF lasting >14 days, and whether plasma NGAL obtained prior to liver transplantation could predict prolonged kidney injury. The studies included 99 deceased kidney donors and their 176 adult recipients and 203 consecutive liver transplant recipients. DGF was seen in 39% of the kidney grafts and the duration of DGF was prolonged in 26 cases. Long-term graft function was significantly decreased in prolonged DGF grafts. NGAL correlated with other markers that describe kidney function such as serum creatinine and GFR. Based on the results measuring serum or urine NGAL the following morning after transplantation predicts DGF and prolonged DGF. Donor urine NGAL correlated with prolonged DGF. In the liver transplant recipients, pretransplant NGAL could not predict posttransplant kidney injury. However, it predicted irreversibility of pretransplant kidney dysfunction, which is helpful in optimizing patient care and deciding whether combined liver-kidney transplantation is needed. In conclusion, measuring blood (serum or plasma) NGAL is useful in assessing kidney function after kidney and liver transplantation.Viivästynyt siirteen käynnistyminen on merkittävä munuaissiirron pitkäaikaisennustetta heikentävä tekijä koskettaen noin kolmannesta munuaissiirroista. Sen ilmaantumista ja kestoa ei voi ennustaa. Sen määrä lisääntyy kun siirrettäväksi hyväksytään yhä vanhempien henkilöiden munuaisia. Maksan vajaatoimintaan liittyy usein myös munuaisten vajaatoiminta. Ennen maksansiirtoa on vaikea ennustaa kenen munuaiset toipuvat ja kuka jää dialyysiriippuvaiseksi maksansiirron jälkeen. Mikäli tätä voitaisiin ennustaa tälle potilasryhmälle voitaisiin tehdä kombinoitu munuaisen ja maksansiirto. NGAL (Neutrophil Gelatinase-Associated Lipocalin) on seerumista ja virtsasta mitattavissa oleva proteiini, jonka on todettu ennustavan akuuttia munuaisten vajaatoimintaa paremmin kuin tällä hetkellä muuten käytössä olevien menetelmien, kuten kreatiniinin. Tässä tutkimuksessa selvitettiin NGAL proteiinin kykyä ennustaa viivästynyttä käyntiinlähtöä, luovuttajan munuaisten laatua, sekä munuaisten vajaatoiminnan kestoa maksansiirron yhteydessä. Varhainen diagnoosi mahdollistaisi yksilöllisen hoidonsuunnittelun ja terapeuttisten interventioiden kehittämisen, jolla viivästynyttä käyntiinlähtöä pystyttäisiin jopa estämään. Munuaissiirtotutkimus koostuu 99 perättäisestä elinluovuttajasta ja heidän munuaistensa vastaanottajista (n=176). Maksatutkimuksessa on mukana kaikki maksansiirtopotilaat vuosilta 2005-2010. NGAL proteiinin pitoisuus määritettiin munuaisten luovuttajien ja vastaanottajien seerumi- ja virtsanäytteistä eri aikapisteissä ja maksansiirtopotilaiden plasmasta ennen maksansiirtoa. Tutkimuksessa 39% munuaissiirteistä käynnistyi viiveellä. Siirteen pitkäaikaisennuste heikkeni merkittävästi kun viivästynyt käyntiinlähtö pitkittyi yli 14vrk kestäväksi. Tutkimuksen tulosten perusteella siirteen käynnistymistä voi ennustaa mittaamalla seerumin ja virtsan NGAL pitoisuutta munuaissiirron jälkeisenä aamuna. Luovuttajan virtsan NGAL korreloi muiden munuaisten toimintaa kuvaavien mittareiden kanssa, kuten seerumin kreatiniini ja GFR. Luovuttajan virtsan NGAL puolestaan ennusti pitkittyvää viivästynyttä käyntiinlähtöä. Sen sijaan seerumin NGAL ei kuvastanut luovuttajan munuaisten toimintaa. Maksansiirtopotilailla ennen siirtoa mitattu plasman NGAL ei ennustanut kenelle kehittyy heti siirron jälkeen munuaisten vajaatoiminta mutta oli riippumaton ennusarvo kenelle munuaisten vajaatoiminta jää pysyväksi siirron jälkeen ja näin voisi auttaa arviossa tarvitaanko kombinaatiosiirto. Veren (seerumin tai plasman) NGAL pitoisuusmääritystä voidaan käyttää arvioitaessa munuaisten toimintaa munuais- ja maksansiirron jälkeen

Trends in Annual Survival of Steller’s Eiders Molting at Izembek Lagoon on the Alaska Peninsula, 1993–2006

Izembek Lagoon, located on the Alaska Peninsula, is an important molting area for the Pacific population of Steller’s Eiders (Polysticta stelleri) and was the site of consistent banding effort during 1993–2006. We used Pradel mark-recapture models to estimate annual survival and population growth rates for adult Steller’s Eiders molting at Izembek Lagoon. We designed 32 models that included effects of sex and year on survival, recapture rate, and seniority, as well as potential trends in survival and seniority. The top model incorporated a two-phase trend (1993–98, 1999–2003) in survival and seniority for each sex and fully sex- and year-specific recapture rates. Average annual adult survival was estimated at 0.86 (SE = 0.030) for females and 0.87 (SE = 0.018) for males. Average annual population growth rates since 1998 were estimated to be approximately 1.0 for both sexes. A brief warming event in the Pacific Decadal Oscillation (1997–98) coincided with the lowest estimates of annual survival, while a subsequent return to cooler conditions in the Bering Sea coincided with the highest estimates and an increasing trend in annual survival.La lagune d’Izembek, située dans la péninsule de l’Alaska, constitue une aire de mue importante pour la population d’eiders de Steller (Polysticta stelleri) du Pacifique. Elle a fait l’objet de travaux de baguage soutenus entre 1993 et 2006. Nous nous sommes servis des modèles de marquage et de recapture de Pradel pour estimer les taux de survie et d’accroissement de la population d’eiders de Steller adultes en période de mue à la lagune d’Izembek. Nous avons conçu 32 modèles qui compre-naient les effets du sexe et de l’année sur le taux de survie, le taux de recapture et l’ancienneté. Le meilleur des modèles comprenait une tendance diphasique (de 1993 à 1998, et de 1999 à 2003) en ce qui a trait aux taux de survie et d’ancienneté de chacun des sexes ainsi qu’en ce qui a trait aux taux de recapture entièrement en fonction du sexe et de l’année. Chez les adultes, le taux de survie moyen était estimé à 0,86 (SE = 0,030) pour la femelle et à 0,87 (SE = 0,018) pour le mâle. Depuis 1998, les taux annuels d’accroissement de la population étaient estimés à environ 1,0 dans le cas des deux sexes. Un bref événement de réchauffement dans l’oscillation décadaire du Pacifique (1997-1998) a coïncidé avec les estimations de survie annuelles les plus faibles, tandis que le retour de conditions plus fraîches dans la mer de Béring a coïncidé avec les estimations les plus élevées ainsi qu’à une tendance à la hausse du taux de survie annuel

Principal Component Analysis Visualizations in State Discovery by Animating Exploration Results

Visualization is a key point in data exploration. In this paper we have emphasis in adding dynamic features by constructing exploration animations. We use Principal Component Analysis (PCA) in dimensionality reduction and Kmeans clustering algorithm in defining states. In predicting state transitions, we use Hidden Markov Model (HMM). Analyzed physical data is got from self-healing autonomous data centers. Our research methodology is to animate state transitions for data exploration in modern computerized environment. We use Jupyter tool and Python 3 programming language in our experimental realization. As results we get PCA animations for exploration purposes. Our approach is based on state discovery, where it is possible to find some physical interpretations for the defined states and state transitions. State structure and behaviour depend strongly on analyzed data.Peer reviewe

Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung

Non peer reviewe

Clever-1 positive macrophages in breast cancer

Purpose Common Lymphatic Endothelial and Vascular Endothelial Receptor 1 (Clever-1) is expressed by a subset of immunosuppressive macrophages and targeting the receptor with therapeutic antibodies has been shown to activate T-cell-mediated anti-cancer immunity. The aim of this research was to study Clever-1 expression in breast cancer. Specifically, how Clever-1 + macrophages correlate with clinicopathologic factors, Tumor Infiltrating Lymphocytes (TILs) and prognosis. Methods Tissue microarray blocks were made from 373 primary breast cancer operation specimens. Hematoxylin and Eosin (H&E-staining) and immunohistochemical staining with Clever-1, CD3, CD4 and CD8 antibodies were performed. Differences in quantities of Clever-1 + macrophages and TILs were analyzed. Clever-1 + cell numbers were correlated with 25-year follow-up survival data and with breast cancer clinicopathologic parameters. Results Low numbers of intratumoral Clever-1 + cells were found to be an independent adverse prognostic sign. Increased numbers of Clever-1 + cells were found in high grade tumors and hormone receptor negative tumors. Tumors that had higher amounts of Clever-1 + cells also tended to have higher amounts of TILs. Conclusion The association of intratumoral Clever-1 + macrophages with better prognosis might stem from the function of Clever as a scavenger receptor that modulates tumor stroma. The association of Clever-1 + macrophages with high number of TILs and better prognosis indicates that immunosuppression by M2 macrophages is not necessarily dampening adaptive immune responses but instead keeping them in control to avoid excess inflammation.Peer reviewe

Serum neutrophil gelatinase-associated lipocalin and recovery of kidney graft function after transplantation

Peer reviewe

Inhibition of Vascular Endothelial Growth Factor Receptors 1 and 2 Attenuates Natural Killer Cell and Innate Immune Responses in an Experimental Model for Obliterative Bronchiolitis

Funding Information: Supported by the Helsinki University Hospital , the Sigrid Juselius Foundation , the Academy of Finland , Finska Läkaresällskapet , the Research and Science Foundation of Farmos , The Paulo Foundation , Jalmari and Rauha Ahokas Foundation , Aarne Koskelo Foundation , Päivi and Sakari Sohlberg Foundation , Finnish Pulmonary Association , Biomedicum Helsinki Foundation , Jane and Aatos Erkko Foundation , and the University of Helsinki . Funding Information: Supported by the Helsinki University Hospital, the Sigrid Juselius Foundation, the Academy of Finland, Finska L?kares?llskapet, the Research and Science Foundation of Farmos, The Paulo Foundation, Jalmari and Rauha Ahokas Foundation, Aarne Koskelo Foundation, P?ivi and Sakari Sohlberg Foundation, Finnish Pulmonary Association, Biomedicum Helsinki Foundation, Jane and Aatos Erkko Foundation, and the University of Helsinki. Publisher Copyright: © 2022 American Society for Investigative PathologyObliterative bronchiolitis (OB) after lung transplantation is a nonreversible, life-threatening complication. Herein, the role of vascular endothelial growth factor receptor (Vegfr)-1 and -2 was investigated in the development of obliterative airway disease (OAD), an experimental model for OB. The nonimmunosuppressed recipients underwent transplantation with fully major histocompatibility complex mismatched heterotopic tracheal allografts and received Vegfr1 and -2-specific monoclonal antibodies either alone or in combination, or rat IgG as a control. The treatment with Vegfr1- or -2-blocking antibody significantly decreased intragraft mRNA expression of natural killer cell activation markers early after transplantation. This was followed by reduced infiltration of Cd11b thorn cells and Cd4 thorn T cells as well as down-regulated mRNA expression of proinflammatory chemokines and profibrotic growth factors. However, blocking of both Vegfr1 and -2 was necessary to reduce luminal occlusion. Furthermore, concomitant inhibition of the calcineurin activation pathway almost totally abolished the development of OAD. This study proposes that blocking of Vegf receptors blunted natural killer cell and innate immune responses early after transplantation and attenuated the development of OAD. The results of this study suggest that further studies on the role of Vegfr1 and -2 blocking in development of obliterative airway lesions might be rewarding. (Am J Pathol 2022, 192: 254-269; https://doi.org/10.1016/ j.ajpath.2021.10.018)Peer reviewe

The tumor and plasma cytokine profiles of renal cell carcinoma patients

Renal cell carcinoma (RCC) accounts for 90% of all renal cancers and is considered highly immunogenic. Although many studies have reported the circulating peripheral cytokine profiles, the signatures between the tumor tissue and matching healthy adjacent renal tissue counterparts have not been explored. We aimed to comprehensively investigate the cytokine landscape of RCC tumors and its correlation between the amount and phenotype of the tumor infiltrating lymphocytes (TILs). We analyzed the secretion of 42 cytokines from the tumor (n = 46), adjacent healthy kidney tissues (n = 23) and matching plasma samples (n = 33) with a Luminex-based assay. We further explored the differences between the tissue types, as well as correlated the findings with clinical data and detailed immunophenotyping of the TILs. Using an unsupervised clustering approach, we observed distinct differences in the cytokine profiles between the tumor and adjacent renal tissue samples. The tumor samples clustered into three distinct profiles based on the cytokine expressions: high (52.2% of the tumors), intermediate (26.1%), and low (21.7%). Most of the tumor cytokines positively correlated with each other, except for IL-8 that showed no correlation with any of the measured cytokine expressions. Furthermore, the quantity of lymphocytes in the tumor samples analyzed with flow cytometry positively correlated with the chemokine-family of cytokines, CXCL10 (IP-10) and CXCL9 (MIG). No significant correlations were found between the tumor and matching plasma cytokines, suggesting that circulating cytokines poorly mirror the tumor cytokine environment. Our study highlights distinct cytokine profiles in the RCC tumor microenvironment and provides insights to potential biomarkers for the treatment of RCC.Peer reviewe

Machine Learning Methods for Neonatal Mortality and Morbidity Classification

Preterm birth is the leading cause of mortality in children under the age of five. In particular, low birth weight and low gestational age are associated with an increased risk of mortality. Preterm birth also increases the risks of several complications, which can increase the risk of death, or cause long-term morbidities with both individual and societal impacts. In this work, we use machine learning for prediction of neonatal mortality as well as neonatal morbidities of bronchopulmonary dysplasia, necrotizing enterocolitis, and retinopathy of prematurity, among very low birth weight infants. Our predictors include time series data and clinical variables collected at the neonatal intensive care unit of Children's Hospital, Helsinki University Hospital. We examine 9 different classifiers and present our main results in AUROC, similar to our previous studies, and in F1-score, which we propose for classifier selection in this study. We also investigate how the predictive performance of the classifiers evolves as the length of time series is increased, and examine the relative importance of different features using the random forest classifier, which we found to generally perform the best in all tasks. Our systematic study also involves different data preprocessing methods which can be used to improve classifier sensitivities. Our best classifier AUROC is 0.922 in the prediction of mortality, 0.899 in the prediction of bronchopulmonary dysplasia, 0.806 in the prediction of necrotizing enterocolitis, and 0.846 in the prediction of retinopathy of prematurity. Our best classifier F1-score is 0.493 in the prediction of mortality, 0.704 in the prediction of bronchopulmonary dysplasia, 0.215 in the prediction of necrotizing enterocolitis, and 0.368 in the prediction of retinopathy of prematurity.Peer reviewe