6,846 research outputs found

    Mice lacking C1q or C3 show accelerated rejection of minor H disparate skin grafts and resistance to induction of tolerance

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    Complement activation is known to have deleterious effects on organ transplantation. On the other hand, the complement system is also known to have an important role in regulating immune responses. The balance between these two opposing effects is critical in the context of transplantation. Here, we report that female mice deficient in C1q (C1qa(−/−)) or C3 (C3(−/−)) reject male syngeneic grafts (HY incompatible) at an accelerated rate compared with WT mice. Intranasal HY peptide administration, which induces tolerance to syngeneic male grafts in WT mice, fails to induce tolerance in C1qa(−/−) or C3(−/−) mice. The rejection of the male grafts correlated with the presence of HY D(b)Uty-specific CD8(+) T cells. Consistent with this, peptide-treated C1qa(−/−) and C3(−/−) female mice rejecting male grafts exhibited more antigen-specific CD8(+)IFN-γ(+) and CD8(+)IL-10(+) cells compared with WT females. This suggests that accumulation of IFN-γ- and IL-10-producing T cells may play a key role in mediating the ongoing inflammatory process and graft rejection. Interestingly, within the tolerized male skin grafts of peptide-treated WT mice, IFN-γ, C1q and C3 mRNA levels were higher compared to control female grafts. These results suggest that C1q and C3 facilitate the induction of intranasal tolerance

    Pediatric Esophageal Dilatations: A Cross-Specialty Experience

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    AIM OF THE STUDY: Esophageal dilatations are commonly performed in pediatric patients who have undergone an esophageal atresia/tracheoesophageal fistula (EA/TEF) repair or following caustic injury. We sought to compare the practice of esophageal dilatation across different specialties. METHODS: We analyzed all patients who had an esophageal dilatation at our center between April 2014 and December 2018. Patients were identified via prospectively maintained databases and clinical coding records. Patients had a combination of dilatations under each specialty: interventional radiology (IR), surgery, and gastroenterology. RESULTS: Thirty-five individual patients underwent 226 dilatations, median dilatations per patient was 3 (1–40). The median age at first dilatation was 18 months (1–194 months). Sixty-eight percent of patients had a previous EA/TEF repair. IR performed 59% of dilatations, surgeons 26%, and 15% by gastroenterologists. Surgeons more frequently were performing initial dilatations (P < .05) and performed more dilatations in EA/TEF patients (P < .0001). There was a significant difference between the time from a surgical dilatation until the next dilatation, 3.7 months, compared with an IR dilatation, 1.8 months (ANOVA, P < .05). Surgeons more frequently increased the size of balloon used (57% versus 33% versus 39%, P < .01). There was no significant difference in balloon size between specialties or in the incremental increase in size between subsequent dilatations. There was one postprocedure perforation, managed conservatively (complication rate = 0.4%). CONCLUSIONS: We have demonstrated that on average, patients wait longer after a surgical dilatation until their next procedure, and surgical teams are more likely to increase the size of the dilating balloon. Surgeons tend to be more involved in their postoperative patients in the initial phases of stricture management. Our results suggest the feasibility and safety of a multispecialty approach for these patients

    Marqueurs chromosomiques: à propos d'un cas

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    Les marqueurs chromosomiques peuvent être définis comme des petits chromosomes de structure anormale présents en addition aux 46 chromosomes humains connus. C'est un groupe hétérogène d'anomalies de structure chromosomique pouvant être avec ou sans conséquence phénotypique. Plusieurs tentatives sont réalisées afin de retrouver une corrélation génotype-phénotype lors de la présence d'un marqueur chromosomique. L'identification du marqueur, son origine et sa structure suit une stratégie bien codifiée actuellement allant d'abord de l'orientation clinique suivie des techniques de cytogénétique conventionnelle (caryotype métaphasique standard, bandes C, NOR) et de cytogénétique moléculaire (M-FISH, CGH, CGH array) puis une détection par des techniques plus ciblées (painting, sondes locus spécifique). Cet ensemble permet une meilleure analyse et correspondance clinico-génétique. Nous rapportons le cas d'un nourrisson présentant une dysmorphie faciale avec un retard psychomoteur dont l'analyse cytogénétique a révélé la présence d'un marqueur chromosomique avec un caryotype métaphasique 47,XX,+mar. A travers cette observation, nous mettons en valeur le rôle de la cytogénétique conventionnelle et moléculaire dans le diagnostic des syndromes dysmorphiques permettant une meilleure prise en charge du patient et un conseil génétique adéquat pour sa familleKey words: Marqueurs chromosomiques, anomalie chromosomique, analyse cytogénétique, dysmorphi

    The rise of the feature documentary : fact or fiction?

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    The last fifteen years have seen the relentless rise of the feature documentary—from four titles released in UK cinemas in 2001 to one hundred and seventeen in 2015. For most documentaries, a short platform cinema release provides the oxygen of press reviews and publicity to drive DVD and VOD sales in an increasingly saturated market. This chapter analyses key trends in documentary distribution by charting the rise of Dogwoof and Picturehouse as two of the UK’s leading documentary distributors. These case studies explore the mechanics of documentary distribution and the clever marketing campaigns used by distributors to create new audiences for documentary beyond its niche market. Dogwoof’s success in home entertainment demonstrates how to develop an engaged audience for documentary despite limited theatrical exposure

    An iterative algorithm for parametrization of shortest length shift registers over finite rings

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    The construction of shortest feedback shift registers for a finite sequence S_1,...,S_N is considered over the finite ring Z_{p^r}. A novel algorithm is presented that yields a parametrization of all shortest feedback shift registers for the sequence of numbers S_1,...,S_N, thus solving an open problem in the literature. The algorithm iteratively processes each number, starting with S_1, and constructs at each step a particular type of minimal Gr\"obner basis. The construction involves a simple update rule at each step which leads to computational efficiency. It is shown that the algorithm simultaneously computes a similar parametrization for the reciprocal sequence S_N,...,S_1.Comment: Submitte

    Origin matters: Using a local reference genome improves measures in population genomics.

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    Genome sequencing enables answering fundamental questions about the genetic basis of adaptation, population structure and epigenetic mechanisms. Yet, we usually need a suitable reference genome for mapping population-level resequencing data. In some model systems, multiple reference genomes are available, giving the challenging task of determining which reference genome best suits the data. Here, we compared the use of two different reference genomes for the three-spined stickleback (Gasterosteus aculeatus), one novel genome derived from a European gynogenetic individual and the published reference genome of a North American individual. Specifically, we investigated the impact of using a local reference versus one generated from a distinct lineage on several common population genomics analyses. Through mapping genome resequencing data of 60 sticklebacks from across Europe and North America, we demonstrate that genetic distance among samples and the reference genomes impacts downstream analyses. Using a local reference genome increased mapping efficiency and genotyping accuracy, effectively retaining more and better data. Despite comparable distributions of the metrics generated across the genome using SNP data (i.e. π, Tajima's D and FST ), window-based statistics using different references resulted in different outlier genes and enriched gene functions. A marker-based analysis of DNA methylation distributions had a comparably high overlap in outlier genes and functions, yet with distinct differences depending on the reference genome. Overall, our results highlight how using a local reference genome decreases reference bias to increase confidence in downstream analyses of the data. Such results have significant implications in all reference-genome-based population genomic analyses

    Optical frequency comb Fourier transform spectroscopy of formaldehyde in the 1250 to 1390 cm−1 range: Experimental line list and improved MARVEL analysis

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    We use optical frequency comb Fourier transform spectroscopy to record high-resolution, low-pressure, room-temperature spectra of formaldehyde (H212C16O) in the range of 1250 to 1390 cm−1. Through line-by-line fitting, we retrieve line positions and intensities of 747 rovibrational transitions: 558 from the ν6 band, 129 from the ν4 band, and 14 from the ν3 band, as well as 46 from four different hot bands. We incorporate the accurate and precise line positions (0.4 MHz median uncertainty) into the MARVEL (measured active vibration-rotation energy levels) analysis of the H2CO spectrum. This increases the number of MARVEL-predicted energy levels by 82 and of rovibrational transitions by 5382, and substantially reduces uncertainties of MARVEL-derived H2CO energy levels over a large range: from pure rotational levels below 200 cm−1 up to multiply excited vibrational levels at 6000 cm−1. This work is an important step toward filling the gaps in formaldehyde data in the HITRAN database
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