Genetic dissection of Anopheles gambiae epithelial responses to gut commensal bacteria

Commensal bacteria inhabiting the mosquito gut have been shown to profoundly influence the outcome of infection with malaria Plasmodium parasites. Genetic variation within mosquito populations has also been associated with the outcome of Plasmodium infections, especially with regard to immune factors, many of them targeting both bacteria and Plasmodium parasites. Although bacteria are considered a major evolutionary force that may affect survival, no link has yet to emerge between mosquito genetic variation and the outcome of bacterial infections. To test this possibility, a model of oral infections was established in Anopheles gambiae, the major malaria vector, with two common members of the mosquito gut microbiota, Asaia and Serratia marcescens. Using genome-wide SNP genotyping and expression analyses, mosquito genes associated with the outcome of Serratia infection and differentially expressed following Asaia or Serratia infection were identified. Three genes encoding type III fibronectin domains (FN3D1-3), associated with the outcome of Serratia infection, were shown to limit Serratia abundance and shift the mosquito gut bacterial population structure by limiting mainly Enterobacteriaceae, suggesting that mosquito responses shape the gut bacterial community with much higher specificity than previously thought. Furthermore, silencing of the gene encoding the gustatory receptor Gr9, also associated with the Serratia infection outcome, was shown to radically increase Serratia levels following oral infection, in a behavioural response than mostly relied on changes in neuropeptide F expression. Both the expression and SNP genotyping analysis indicated the existence of an epithelial and a behavioural mode of immunity following oral bacterial infection and revealed the complexity and specificity of this intricate biological system that is expected to shape malaria transmission dynamics.Open Acces

Esophageal and small bowel obstruction by occupational bezoar: report of a case

BACKGROUND: Phytobezoar may be a cause of bowel obstruction in patients with previous gastric surgery. Most bezoars are concretions of poorly digested food, which are usually formed initially in the stomach. Intestinal obstruction (esophageal and small bowel) caused by an occupational bezoar has not been reported. CASE PRESENTATION: A 70-year old male is presented suffering from esophageal and small bowel obstruction, caused by an occupational bezoar. The patient has worked as a carpenter for 35 years. He had undergone a vagotomy and pyloroplasty 10 years earlier. The part of the bezoar, which caused the esophageal obstruction was removed during endoscopy, while the part of the small bowel was treated surgically. The patient recovered well and was discharged on the 8(th )postoperative day. CONCLUSIONS: Since occupational bezoars may be a cause of intestinal obstruction (esophageal and/or small bowel), patients who have undergone a previous gastric surgery should avoid occupational exposures similar to the presented case

Similar patterns of tropical precipitation and circulation changes under solar and greenhouse gas forcing

Funder: "Cosmic and electric effects on aerosols and clouds”; Grant(s): (MIS: 5049552)Funder: Villum Fonden; doi: http://dx.doi.org/10.13039/100008398Abstract: Theory and model evidence indicate a higher global hydrological sensitivity for the same amount of surface warming to solar as to greenhouse gas (GHG) forcing, but regional patterns are highly uncertain due to their dependence on circulation and dynamics. We analyse a multi-model ensemble of idealized experiments and a set of simulations of the last millennium and we demonstrate similar global signatures and patterns of forced response in the tropical Pacific, of higher sensitivity for the solar forcing. In the idealized simulations, both solar and GHG forcing warm the equatorial Pacific, enhance precipitation in the central Pacific, and weaken and shift the Walker circulation eastward. Centennial variations in the solar forcing over the last millennium cause similar patterns of enhanced equatorial precipitation and slowdown of the Walker circulation in response to periods with stronger solar forcing. Similar forced patterns albeit of considerably weaker magnitude are identified for variations in GHG concentrations over the 20th century, with the lower sensitivity explained by fast atmospheric adjustments. These findings differ from previous studies that have typically suggested divergent responses in tropical precipitation and circulation between the solar and GHG forcings. We conclude that tropical Walker circulation and precipitation might be more susceptible to solar variability rather than GHG variations during the last-millennium, assuming comparable global mean surface temperature changes

Study of the interactions of suspended particles and clouds over large urban agglomerations in SE Asia and over the Eastern Mediterranean

The aim of this thesis was to investigate the interactions between particulate matter and clouds over large urban agglomerations in Southeast Asia and over East Mediterranean. It is organized in four chapters, each of which represents a different approach to examine the relations between particulate matter and clouds, over the study area.In Chapter 1, the relations between Aerosol Optical Depth (AOD), Cloud Cover (CC) and Cloud Top Pressure (CTP), under different Sea Level Pressure (SLP) and Water Vapor (WV) regimes, over three major urban clusters in China, were investigated, using remote sensing data from Moderate Resolution Imaging Spectroradiometer (MODIS) sensor. Over all urban clusters and for all SLP regimes, CC was found to increase with increasing AOD, pointing out that the CC dependence on AOD cannot be explained by synoptic covariation alone. In addition, WV was found to have a stronger impact on CC than AOD, which is more pronounced at high aerosol load. Hence, studies that investigate the AOD-CC relations and are based on satellite data will overestimate (underestimate) the AOD impact on CC in regions where AOD and WV have similar (opposite) seasonal variations.In Chapter 2, the aerosol-cloud relations over the same three urban clusters in China, under different WV conditions and cloud heights were investigated, using AOD, CC, WV, CTP and Cloud Optical Depth (COD) data from the MODIS sensor. Over all regions and for all seasons, CC was found to increase with increasing AOD, WV and cloud height. In addition, AOD, at low WV environments and under constant CTP, was found to have less impact on CC than at high WV environments. Furthermore, AOD was observed to have a varying influence on COD depending on CTP, while COD was found to increase with height for low and middle height clouds, and with increasing AOD, especially at low AOD regimes.In Chapter 3, the causal links between aerosols, water vapor and clouds were investigated, using the Convergent Cross Mapping (CCM) method, utilizing remote sensing data of AOD, WV, CC, COD, Cloud Effective Radius-Ice (CERI) and Cloud Effective Radius-Liquid (CERL) from MODIS sensor, over East Asia. The analysis showed that there is a bidirectional forcing between AOD, CC and COD which could be attributed to the invigoration effect of aerosols on clouds. In addition, it was found that there is a bidirectional forcing between AOD-WV and AOD-CERL, which could be attributed to the first indirect effect of aerosols on clouds, while there is no causality among AOD and CERI, probably because of strong coupling among aerosols and ice nuclei. Finally, based on the analysis, it was inferred that CCM method can effectively be used in all aerosol-cloud relations studies, searching for causality among the parameters.In Chapter 4, the annual and seasonal aerosol-cloud relations were investigated, under different WV conditions, over nine subregions of the Eastern Mediterranean region, utilizing remote sensing data of AOD, WV, CC, COD and CTP from MODIS sensor. In addition, anthropogenic AOD (AODanthr) and dust AOD (AODdust) data that were produced within the QUantifying the Aerosol Direct and Indirect Effect over Eastern Mediterranean (QUADIEEMS) research project were used as well. Over all regions, seasons and WV bins, CC was found to increase with increasing total, anthropogenic aerosol and dust loading, pointing towards the aerosol invigoration effect on clouds. For AOD0.5 to decrease or remain constant, irrespective of WV amount. In addition, over all regions and for all seasons, anthropogenic COD was observed to be larger than dust COD. CTP in spring and summer months was found to decrease with increasing AOD and CC, while in autumn and winter months and for high WV concentrations, CTP increased with increasing aerosol loading. Finally, clouds over land were found to be higher than clouds over the nearby sea.Σκοπός της παρούσας διδακτορικής διατριβής ήταν να διερευνηθούν οι αλληλεπιδράσεις των αιωρούμενων σωματιδίων και νεφών πάνω από μεγάλα αστικά συσσωματώματα της Νοτιοανατολικής Ασίας και πάνω από την περιοχή της Ανατολικής Μεσογείου. Είναι οργανωμένη σε τέσσερα κεφάλαια, καθένα από τα οποία περιέχει μια διαφορετική προσέγγιση για τη μελέτη της σχέσης μεταξύ αιωρούμενων σωματιδίων και νεφών, πάνω από την υπο-μελέτη περιοχή.Στο Κεφάλαιο 1, μελετήθηκαν οι σχέσεις μεταξύ του Οπτικού Βάθους Αερολυμάτων (AOD), της Νεφοκάλυψης (CC) και της Πίεσης στην Κορυφή του Νέφους (CTP), κάτω από διαφορετικές συνθήκες Πίεσης στην Επιφάνεια της Θάλασσας (SLP) και Υδρατμών (WV), πάνω από τρία μεγάλα αστικά συσσωματώματα της Κίνας, χρησιμοποιώντας δορυφορικά δεδομένα από το Εικονοληπτικό Φασματοραδιόμετρο Μέσης Ανάλυσης (MODIS). Πάνω από όλες τις περιοχές και για όλες τις συνθήκες SLP, το CC βρέθηκε να αυξάνει για αυξανόμενο AOD, υποδεικνύοντας ότι η εξάρτηση του CC στο AOD δεν μπορεί να ερμηνευτεί μόνο λόγω συνδιακύμανσης των συνοπτικών συνθηκών. Επιπλέον, το WV βρέθηκε να έχει μεγαλύτερη επίδραση στο CC από ότι στο AOD, κυρίως σε περιβάλλοντα με αυξημένες συγκεντρώσεις αερολυμάτων. Για το λόγο αυτό, μελέτες που ερευνούν τις σχέσεις μεταξύ AOD-CC και βασίζονται σε δορυφορικά δεδομένα ενδέχεται να υπερεκτιμήσουν (υποεκτιμήσουν) την επίδραση του AOD στο CC, σε περιοχές όπου το AOD και το WV έχουν παρόμοιες (αντίθετες) εποχικές μεταβολές.Στο Κεφάλαιο 2, μελετήθηκαν οι σχέσεις μεταξύ των αερολυμάτων και των νεφών, πάνω από τις ίδιες περιοχές, όπως στο Κεφάλαιο 1, για διαφορετικές ποσότητες WV και για διαφορετικά ύψη νεφών, χρησιμοποιώντας δορυφορικά δεδομένα AOD, CC, WV, CTP και Οπτικού Βάθους Νεφών (COD) από το όργανο MODIS. Πάνω από όλες τις περιοχές και για όλες τις εποχές, το CC βρέθηκε να αυξάνει για αυξανόμενο AOD, WV και ύψος νεφών. Επίσης, το οπτικό βάθος των αερολυμάτων σε περιβάλλοντα με χαμηλό WV και σταθερό CTP, βρέθηκε να έχει μικρότερη επίδραση στο CC, από ότι σε περιβάλλοντα με υψηλό WV. Επιπλέον, παρατηρήθηκε ότι η επίδραση του AOD στο COD μεταβάλλεται ανάλογα με το CTP, ενώ το COD, για αυξανόμενο AOD, βρέθηκε να αυξάνεται με το ύψος, για χαμηλά και μεσαίου ύψους νέφη, κυρίως σε συνθήκες χαμηλού AOD.Στο Κεφάλαιο 3, ερευνήθηκαν οι αιτιώδεις σχέσεις μεταξύ αερολυμάτων, υδρατμών στην ατμόσφαιρα και νεφών, χρησιμοποιώντας τη μέθοδο της Συγκλίνουσας Σταυρωτής Απεικόνισης (CCM), σε συνδυασμό με δορυφορικά δεδομένα AOD, WV, CC, COD, Ενεργής Διαμέτρου Παγωμένων Σωματιδίων του Νέφους (CERI) και Ενεργής Διαμέτρου Υγρών Σωματιδίων του Νέφους (CERL) από τον αισθητήρα MODIS, πάνω από την περιοχή της Ανατολικής Ασίας. Η ανάλυση έδειξε ότι υπάρχει αμφίδρομη επίδραση μεταξύ AOD, CC και COD, η οποία μπορεί να αποδοθεί στην ενισχυτική επίδραση των αερολυμάτων στα νέφη. Επιπλέον, βρέθηκε αμφίδρομη επίδραση μεταξύ AOD-WV και AOD-CERL, που μπορεί να αποδοθεί στην πρώτη έμμεση επίδραση των αερολυμάτων στα νέφη, ενώ δεν βρέθηκε αιτιώδης σχέση μεταξύ AOD και CERI, πιθανώς λόγω της ισχυρής σύζευξης μεταξύ των αερολυμάτων και των παγωμένων σωματιδίων. Τέλος, με βάση την παραπάνω ανάλυση, εξάγεται το συμπέρασμα ότι η μέθοδος CCM, μπορεί να χρησιμοποιηθεί αποτελεσματικά σε μελέτες που διερευνούν την αιτιότητα μεταξύ αερολυμάτων και παραμέτρων των νεφών.Στο Κεφάλαιο 4, διερευνήθηκαν οι ετήσιες και εποχικές σχέσεις μεταξύ των αερολυμάτων και των νεφών, για διαφορετικές συνθήκες WV, πάνω από εννέα υποπεριοχές της Ανατολικής Μεσογείου. Χρησιμοποιήθηκαν δορυφορικά δεδομένα AOD, WV, CC, COD και CTP από τον αισθητήρα MODIS, μαζί με δεδομένα AOD από ανθρωπογενή αερολύματα (AODanthr) και AOD από σκόνη (AODdust), τα οποία παράχθηκαν στα πλαίσια του προγράμματος “Ποσοτικοποίηση της Άμεσης και Έμμεσης Επίδρασης των Αερολυμάτων Πάνω Από την Ανατολική Μεσόγειο” (QUADIEEMS). Πάνω από όλες τις περιοχές, για όλες τις εποχές και για όλα τα σύνολα WV, το CC βρέθηκε να αυξάνει για αυξανόμενη συγκέντρωση ολικών και ανθρωπογενών αερολυμάτων και σκόνης, υποδεικνύοντας την ενισχυτική επίδραση των αερολυμάτων στα νέφη. Για AOD0,5 να μειώνεται ή να παραμένει σταθερό, ανεξάρτητα από το WV. Επιπλέον, πάνω από όλες τις περιοχές και για όλες τις εποχές, το COD λόγω ανθρωπογενών αερολυμάτων βρέθηκε να είναι μεγαλύτερο από το αντίστοιχο λόγω σκόνης. Ακόμα, παρατηρήθηκε ότι το CTP κατά τη διάρκεια της άνοιξης και του καλοκαιριού μειώνεται όσο αυξάνεται το AOD και το CC, ενώ κατά τη διάρκεια του φθινοπώρου και του χειμώνα και για υψηλό WV να αυξάνεται. Τέλος, βρέθηκε ότι τα νέφη πάνω από τις ηπειρωτικές περιοχές βρίσκονται σε μεγαλύτερο ύψος από ότι πάνω από τις θαλάσσιες

Adult Patients with Cancer Have Impaired Humoral Responses to Complete and Booster COVID-19 Vaccination, Especially Those with Hematologic Cancer on Active Treatment: A Systematic Review and Meta-Analysis

The exclusion of patients with cancer in clinical trials evaluating COVID-19 vaccine efficacy and safety, in combination with the high rate of severe infections, highlights the need for optimizing vaccination strategies. The aim of this study was to perform a systematic review and meta-analysis of the published available data from prospective and retrospective cohort studies that included patients with either solid or hematological malignancies according to the PRISMA Guidelines. A literature search was performed in the following databases: Medline (Pubmed), Scopus, Clinicaltrials.gov, EMBASE, CENTRAL and Google Scholar. Overall, 70 studies were included for the first and second vaccine dose and 60 studies for the third dose. The Effect Size (ES) of the seroconversion rate after the first dose was 0.41 (95%CI: 0.33–0.50) for hematological malignancies and 0.56 (95%CI: 0.47–0.64) for solid tumors. The seroconversion rates after the second dose were 0.62 (95%CI: 0.57–0.67) for hematological malignancies and 0.88 (95%CI: 0.82–0.93) for solid tumors. After the third dose, the ES for seroconversion was estimated at 0.63 (95%CI: 0.54–0.72) for hematological cancer and 0.88 (95%CI: 0.75–0.97) for solid tumors. A subgroup analysis was performed to evaluate potential factors affecting immune response. Production of anti-SARS-CoV-2 antibodies was found to be more affected in patients with hematological malignancies, which was attributed to the type of malignancy and treatment with monoclonal antibodies according to the subgroup analyses. Overall, this study highlights that patients with cancer present suboptimal humoral responses after COVID-19 vaccination. Several factors including timing of vaccination in relevance with active therapy, type of therapy, and type of cancer should be considered throughout the immunization process

Genetic dissection of Anopheles gambiae gut epithelial responses to Serratia marcescens.

Genetic variation in the mosquito Anopheles gambiae profoundly influences its ability to transmit malaria. Mosquito gut bacteria are shown to influence the outcome of infections with Plasmodium parasites and are also thought to exert a strong drive on genetic variation through natural selection; however, a link between antibacterial effects and genetic variation is yet to emerge. Here, we combined SNP genotyping and expression profiling with phenotypic analyses of candidate genes by RNAi-mediated silencing and 454 pyrosequencing to investigate this intricate biological system. We identified 138 An. gambiae genes to be genetically associated with the outcome of Serratia marcescens infection, including the peptidoglycan recognition receptor PGRPLC that triggers activation of the antibacterial IMD/REL2 pathway and the epidermal growth factor receptor EGFR. Silencing of three genes encoding type III fibronectin domain proteins (FN3Ds) increased the Serratia load and altered the gut microbiota composition in favor of Enterobacteriaceae. These data suggest that natural genetic variation in immune-related genes can shape the bacterial population structure of the mosquito gut with high specificity. Importantly, FN3D2 encodes a homolog of the hypervariable pattern recognition receptor Dscam, suggesting that pathogen-specific recognition may involve a broader family of immune factors. Additionally, we showed that silencing the gene encoding the gustatory receptor Gr9 that is also associated with the Serratia infection phenotype drastically increased Serratia levels. The Gr9 antibacterial activity appears to be related to mosquito feeding behavior and to mostly rely on changes of neuropeptide F expression, together suggesting a behavioral immune response following Serratia infection. Our findings reveal that the mosquito response to oral Serratia infection comprises both an epithelial and a behavioral immune component

Mammalian PNLDC1 is a novel poly(A) specific exonuclease with discrete expression during early development

PNLDC1 is a homologue of poly(A) specific ribonuclease (PARN), a known deadenylase with additional role in processing of non-coding RNAs. Both enzymes were reported recently to participate in piRNA biogenesis in silkworm and C. elegans, respectively. To get insights on the role of mammalian PNLDC1, we characterized the human and mouse enzymes. PNLDC1 shows limited conservation compared to PARN and represents an evolutionary related but distinct group of enzymes. It is expressed specifically in mouse embryonic stem cells, human and mouse testes and during early mouse embryo development, while it fades during differentiation. Its expression in differentiated cells, is suppressed through methylation of its promoter by the de novo methyltransferase DNMT3B. Both enzymes are localized mainly in the ER and exhibit in vitro specificity restricted solely to 3' RNA or DNA polyadenylates. Knockdown of Pnldc1 in mESCs and subsequent NGS analysis showed that although the expression of the remaining deadenylases remains unaffected, it affects genes involved mainly in reprogramming, cell cycle and translational regulation. Mammalian PNLDC1 is a novel deadenylase expressed specifically in cell types which share regulatory mechanisms required for multipotency maintenance. Moreover, it could be involved both in posttranscriptional regulation through deadenylation and genome surveillance during early development.</p

Mapping of <i>An. gambiae</i> genetic variation associated with the <i>S. marcescens</i> infection phenotype.

<p>SNPs with MAF difference >0.5 and 10-SNP windows with Bonferroni-corrected significance (p-value<10⁻⁵) are shown in their respective chromosomal position as red X crosses and dots, respectively. Non-significant 10-SNP windows are shown as blue dots. Genomic areas with highlighted SNPs and/or significant 10-SNP windows in close proximity are referred to as peaks and are numbered. Each peak is referred to using the chromosomal arms it resides on and its respective assigned number. The genomic positions of genes of interest found within a 5 kb radius of highlighted SNPs or within genomic areas delineated by 10-SNP windows with a significant p-value are indicated by vertical arrows.</p