Mining for single nucleotide polymorphisms in pig genome sequence data

<p>Abstract</p> <p>Background</p> <p>Single nucleotide polymorphisms (SNPs) are ideal genetic markers due to their high abundance and the highly automated way in which SNPs are detected and SNP assays are performed. The number of SNPs identified in the pig thus far is still limited.</p> <p>Results</p> <p>A total of 4.8 million whole genome shotgun sequences obtained from the NCBI trace-repository with center name "SDJVP", and project name "Sino-Danish Pig Genome Project" were analysed for the presence of SNPs. Available BAC and BAC-end sequences and their naming and mapping information, all obtained from SangerInstitute FTP site, served as a rough assembly of a reference genome. In 1.2 Gb of pig genome sequence, we identified 98,151 SNPs in which one of the sequences in the alignment represented the polymorphism and 6,374 SNPs in which two sequences represent an identical polymorphism. To benchmark the SNP identification method, 163 SNPs, in which the polymorphism was represented twice in the sequence alignment, were selected and tested on a panel of three purebred boar lines and wild boar. Of these 163 in silico identified SNPs, 134 were shown to be polymorphic in our animal panel.</p> <p>Conclusion</p> <p>This SNP identification method, which mines for SNPs in publicly available porcine shotgun sequences repositories, provides thousands of high quality SNPs. Benchmarking in an animal panel showed that more than 80% of the predicted SNPs represented true genetic variation.</p

Circulating levels of insulin-like growth factor-I (IGF-I) correlate with disease status in leprosy

<p>Abstract</p> <p>Background</p> <p>Caused by <it>Mycobacterium leprae </it>(ML), leprosy presents a strong immune-inflammatory component, whose status dictates both the clinical form of the disease and the occurrence of reactional episodes. Evidence has shown that, during the immune-inflammatory response to infection, the growth hormone/insulin-like growth factor-I (GH/IGF-I) plays a prominent regulatory role. However, in leprosy, little, if anything, is known about the interaction between the immune and neuroendocrine systems.</p> <p>Methods</p> <p>In the present retrospective study, we measured the serum levels of IGF-I and IGBP-3, its major binding protein. These measurements were taken at diagnosis in nonreactional borderline tuberculoid (NR BT), borderline lepromatous (NR BL), and lepromatous (NR LL) leprosy patients in addition to healthy controls (HC). LL and BL patients who developed reaction during the course of the disease were also included in the study. The serum levels of IGF-I, IGFBP-3 and tumor necrosis factor-alpha (TNF-α) were evaluated at diagnosis and during development of reversal (RR) or erythema nodosum leprosum (ENL) reaction by the solid phase, enzyme-labeled, chemiluminescent-immunometric method.</p> <p>Results</p> <p>The circulating IGF-I/IGFBP-3 levels showed significant differences according to disease status and occurrence of reactional episodes. At the time of leprosy diagnosis, significantly lower levels of circulating IGF-I/IGFBP-3 were found in NR BL and NR LL patients in contrast to NR BT patients and HCs. However, after treatment, serum IGF-I levels in BL/LL patients returned to normal. Notably, the levels of circulating IGF-I at diagnosis were low in 75% of patients who did not undergo ENL during treatment (NR LL patients) in opposition to the normal levels observed in those who suffered ENL during treatment (R LL patients). Nonetheless, during ENL episodes, the levels observed in RLL sera tended to decrease, attaining similar levels to those found in NR LL patients. Interestingly, IGF-I behaved contrary to what was observed during RR episodes in R BL patients.</p> <p>Conclusions</p> <p>Our data revealed important alterations in the IGF system in relation to the status of the host immune-inflammatory response to ML while at the same time pointing to the circulating IGF-I/IGFBP-3 levels as possible predictive biomarkers for ENL in LL patients at diagnosis.</p

Regulatory (pan-)genome of an obligate intracellular pathogen in the PVC superphylum.

Like other obligate intracellular bacteria, the Chlamydiae feature a compact regulatory genome that remains uncharted owing to poor genetic tractability. Exploiting the reduced number of transcription factors (TFs) encoded in the chlamydial (pan-)genome as a model for TF control supporting the intracellular lifestyle, we determined the conserved landscape of TF specificities by ChIP-Seq (chromatin immunoprecipitation-sequencing) in the chlamydial pathogen Waddlia chondrophila. Among 10 conserved TFs, Euo emerged as a master TF targeting &gt;100 promoters through conserved residues in a DNA excisionase-like winged helix-turn-helix-like (wHTH) fold. Minimal target (Euo) boxes were found in conserved developmentally-regulated genes governing vertical genome transmission (cytokinesis and DNA replication) and genome plasticity (transposases). Our ChIP-Seq analysis with intracellular bacteria not only reveals that global TF regulation is maintained in the reduced regulatory genomes of Chlamydiae, but also predicts that master TFs interpret genomic information in the obligate intracellular α-proteobacteria, including the rickettsiae, from which modern day mitochondria evolved

Control of Visceral Leishmaniasis in Latin America—A Systematic Review

Visceral leishmaniasis is a vector-borne disease characterized by fever, spleen and liver enlargement, and low blood cell counts. In the Americas VL is zoonotic, with domestic dogs as main animal reservoirs, and is caused by the intracellular parasite Leishmania infantum (syn. Leishmania chagasi). Humans acquire the infection through the bite of an infected sand fly. The disease is potentially lethal if untreated. VL is reported from Mexico to Argentina, with recent trends showing a rapid spread in Brazil. Control measures directed against the canine reservoir and insect vectors have been unsuccessful, and early detection and treatment of human cases remains as the most important strategy to reduce case fatality. Well-designed studies evaluating diagnosis, treatment, and prevention/control interventions are scarce. The available scientific evidence reasonably supports the use of rapid diagnostic tests for the diagnosis of human disease. Properly designed randomized controlled trials following good clinical practices are needed to inform drug policy. Routine control strategies against the canine reservoirs and insect vectors are based on weak and conflicting evidence, and vector control strategies and vaccine development should constitute research priorities

Mitophagy plays a central role in mitochondrial ageing

The mechanisms underlying ageing have been discussed for decades, and advances in molecular and cell biology of the last three decades have accelerated research in this area. Over this period, it has become clear that mitochondrial function, which plays a major role in many cellular pathways from ATP production to nuclear gene expression and epigenetics alterations, declines with age. The emerging concepts suggest novel mechanisms, involving mtDNA quality, mitochondrial dynamics or mitochondrial quality control. In this review, we discuss the impact of mitochondria in the ageing process, the role of mitochondria in reactive oxygen species production, in nuclear gene expression, the accumulation of mtDNA damage and the importance of mitochondrial dynamics and recycling. Declining mitophagy (mitochondrial quality control) may be an important component of human ageing

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Designing an AI-companion to support the driver in highly autonomous cars

In this paper, we propose a model for an AI-Companion for conditionally automated cars, able to maintain awareness of the driver regarding the environment but also to able design take-over requests (TOR) on the fly, with the goal of better support the driver in case of a disengagement. Our AI-Companion would interact with the driver in two ways: first, it could provide feedback to the driver in order to raise the driver Situation Awareness (SA), prevent them to get out of the supervision loop and so, improve takeover during critical situations by decreasing their cognitive workload. Second, in the case of TOR with a smart choice of modalities for convey the request to the driver. In particular, the AI-Companion can interact with the driver using many modalities, such as visual messages (warning lights, images, text, etc.), auditory signals (sound, speech, etc.) and haptic technologies (vibrations in different parts of the seat: back, headrest, etc.). The ultimate goal of the proposed approach is to design smart HMIs in semi-autonomous vehicles that are able to understand 1) the user state and fitness to drive, 2) the current external situation (vehicle status and behavior) in order to minimize the automation surprise and maximizing safety and trust, and 3) leverage AI to provide adaptive TOR and useful feedback to the driver