Relapsing sepsis episodes of Escherichia coli with CTX-M ESBL or derepressed ampC genes in a patient with chronic autoimmune pancreatitis complicated by IgG4 hypergammaglobulinaemia

Bloodstream recurrent infections have been reported for a variety of opportunistic bacteria. These are often either catheter related or are caused by indwelling devices. A case of relapsing sepsis with two Escherichia coli strains carrying extended-spectrum β-lactamase and derepressed ampC genes is reported. The patient had seven episodes of bloodstream infections within 1 year and was diagnosed with chronic autoimmune pancreatitis and IgG4 hypergammaglobulinaemia. Abscesses were found in his spleen and pancreas cauda, which was finally resected. Relapses of bacteraemia with resistant enterobacteria should be considered during perioperative protection. Surgical removal of the infective focus could be curative.Peer reviewe

Novel flaviviruses from mosquitoes: Mosquito-specific evolutionary lineages within the phylogenetic group of mosquito-borne flaviviruses

Copyright © 2014 The Authors. Published by Elsevier Inc. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. The attached file is the published version of the article

Viral RNA Metagenomics of Hyalomma Ticks Collected from Dromedary Camels in Makkah Province, Saudi Arabia

Arthropod-borne infections are a medical and economic threat to humans and livestock. Over the last three decades, several unprecedented viral outbreaks have been recorded in the Western part of the Arabian Peninsula. However, little is known about the circulation and diversity of arthropod-borne viruses in this region. To prepare for new outbreaks of vector-borne diseases, it is important to detect which viruses circulate in each vector population. In this study, we used a metagenomics approach to characterize the RNA virome of ticks infesting dromedary camels (Camelus dromedaries) in Makkah province, Saudi Arabia. Two hundred ticks of species Hyalomma dromedarii (n = 196) and Hyalomma impeltatum (n = 4) were collected from the Alkhurma district in Jeddah and Al-Taif city. Virome analysis showed the presence of several tick-specific viruses and tick-borne viruses associated with severe illness in humans. Some were identified for the first time in the Arabian Peninsula. The human disease-associated viruses detected included Crimean Congo Hemorrhagic fever virus and Tamdy virus (family Nairoviridae), Guertu virus (family Phenuiviridae), and a novel coltivirus that shares similarities with Tarumizu virus, Tai forest reovirus and Kundal virus (family Reoviridae). Furthermore, Alkhurma hemorrhagic virus (Flaviviridae) was detected in two tick pools by specific qPCR. In addition, tick-specific viruses in families Phenuiviridae (phleboviruses), Iflaviridae, Chuviridae, Totiviridae and Flaviviridae (Pestivirus) were detected. The presence of human pathogenetic viruses warrants further efforts in tick surveillance, xenosurveillence, vector control, and sero-epidemiological investigations in human and animal populations to predict, contain and mitigate future outbreaks in the region

Viral RNA Metagenomics of Hyalomma Ticks Collected from Dromedary Camels in Makkah Province, Saudi Arabia

Arthropod-borne infections are a medical and economic threat to humans and livestock. Over the last three decades, several unprecedented viral outbreaks have been recorded in the Western part of the Arabian Peninsula. However, little is known about the circulation and diversity of arthropod-borne viruses in this region. To prepare for new outbreaks of vector-borne diseases, it is important to detect which viruses circulate in each vector population. In this study, we used a metagenomics approach to characterize the RNA virome of ticks infesting dromedary camels (Camelus dromedaries) in Makkah province, Saudi Arabia. Two hundred ticks of species Hyalomma dromedarii (n = 196) and Hyalomma impeltatum (n = 4) were collected from the Alkhurma district in Jeddah and Al-Taif city. Virome analysis showed the presence of several tick-specific viruses and tick-borne viruses associated with severe illness in humans. Some were identified for the first time in the Arabian Peninsula. The human disease-associated viruses detected included Crimean Congo Hemorrhagic fever virus and Tamdy virus (family Nairoviridae), Guertu virus (family Phenuiviridae), and a novel coltivirus that shares similarities with Tarumizu virus, Tai forest reovirus and Kundal virus (family Reoviridae). Furthermore, Alkhurma hemorrhagic virus (Flaviviridae) was detected in two tick pools by specific qPCR. In addition, tick-specific viruses in families Phenuiviridae (phleboviruses), Iflaviridae, Chuviridae, Totiviridae and Flaviviridae (Pestivirus) were detected. The presence of human pathogenetic viruses warrants further efforts in tick surveillance, xenosurveillence, vector control, and sero-epidemiological investigations in human and animal populations to predict, contain and mitigate future outbreaks in the region

CFAP300 mutation causing primary ciliary dyskinesia in Finland

Primary ciliary dyskinesia (PCD) is a rare genetic condition characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell that are responsible for removal of mucus from the airways and organizing internal organ positioning during embryonic development. PCD is caused by mutations in genes coding for structural or assembly proteins in motile cilia. Thus far mutations in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported, thus highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics. In this study, we identified a recurrent loss-of-function mutation c.198_200delinsCC in CFAP300 causing lack of the protein product. PCD patients homozygous for the identified CFAP300 mutation have immotile airway epithelial cilia associated with missing dynein arms in their ciliary axonemes. Furthermore, using super resolution microscopy we demonstrate that CFAP300 is transported along cilia in normal human airway epithelial cells suggesting a role for CFAP300 in dynein complex transport in addition to preassembly in the cytoplasm. Our results highlight the importance of CFAP300 in dynein arm assembly and improve diagnostics of PCD in Finland.publishedVersionPeer reviewe

Whole-genome SNP association analysis of reproduction traits in the Finnish Landrace pig breed

<p>Abstract</p> <p>Background</p> <p>Good genetic progress for pig reproduction traits has been achieved using a quantitative genetics-based multi-trait BLUP evaluation system. At present, whole-genome single nucleotide polymorphisms (SNP) panels provide a new tool for pig selection. The purpose of this study was to identify SNP associated with reproduction traits in the Finnish Landrace pig breed using the Illumina PorcineSNP60 BeadChip.</p> <p>Methods</p> <p>Association of each SNP with different traits was tested with a weighted linear model, using SNP genotype as a covariate and animal as a random variable. Deregressed estimated breeding values of the progeny tested boars were used as the dependent variable and weights were based on their reliabilities. Statistical significance of the associations was based on Bonferroni-corrected <it>P</it>-values.</p> <p>Results</p> <p>Deregressed estimated breeding values were available for 328 genotyped boars. Of the 62 163 SNP in the chip, 57 868 SNP had a call rate > 0.9 and 7 632 SNP were monomorphic. Statistically significant results (<it>P</it>-value < 2.0E-06) were obtained for total number of piglets born in first and later parities and piglet mortality between birth and weaning in later parity, and suggestive associations (<it>P</it>-value < 4.0E-06) for piglet mortality between birth and weaning in first parity, number of stillborn piglets in later parity, first farrowing interval and second farrowing interval. Two of the statistically significant regions for total number of piglets born in first and later parities are located on chromosome 9 around 95 and 79 Mb. The estimated SNP effect in these regions was approximately one piglet between the two homozygote classes. By combining the two most significant SNP in these regions, favourable double homozygote animals are expected to have 1.3 piglets (<it>P</it>-value = 1.69E-08) more than unfavourable double homozygote animals. A region on chromosome 9 (66 Mb) was statistically significant for piglet mortality between birth and weaning in later parity (0.44 piglets between homozygotes, <it>P</it>-value = 6.94E-08).</p> <p>Conclusions</p> <p>Three separate regions on chromosome 9 gave significant results for litter size and pig mortality. The frequencies of favourable alleles of the significant SNP are moderate in the Finnish Landrace population and these SNP are thus valuable candidates for possible marker-assisted selection.</p

A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs

Ciliopathies presenting as inherited hepatorenal fibrocystic disorders are rare in humans and in dogs. We describe here a novel lethal ciliopathy in Norwich Terrier puppies that was diagnosed at necropsy and characterized as diffuse cystic renal disease and hepatic fibrosis. The histopathological findings were typical for cystic renal dysplasia in which the cysts were located in the straight portion of the proximal tubule, and thin descending and ascending limbs of Henle’s loop. The pedigree of the affected puppies was suggestive of an autosomal recessive inheritance and therefore, whole exome sequencing and homozygosity mapping were used for identification of the causative variant. The analyses revealed a case-specific homozygous splice donor site variant in a cilia related gene, INPP5E: c.1572+5G>A. Association of the variant with the defect was validated in a large cohort of Norwich Terriers with 3 cases and 480 controls, the carrier frequency being 6%. We observed that the identified variant introduces a novel splice site in INPP5E causing a frameshift and formation of a premature stop codon. In conclusion, our results suggest that the INPP5E: c.1572+5G>A variant is causal for the ciliopathy in Norwich Terriers. Therefore, genetic testing can be carried out in the future for the eradication of the disease from the breed

Towards a coordinated strategy for intercepting human disease emergence in Africa

Non peer reviewe

MNS1 Is Essential for Spermiogenesis and Motile Ciliary Functions in Mice

During spermiogenesis, haploid round spermatids undergo dramatic cell differentiation and morphogenesis to give rise to mature spermatozoa for fertilization, including nuclear elongation, chromatin remodeling, acrosome formation, and development of flagella. The molecular mechanisms underlining these fundamental processes remain poorly understood. Here, we report that MNS1, a coiled-coil protein of unknown function, is essential for spermiogenesis. We find that MNS1 is expressed in the germ cells in the testes and localizes to sperm flagella in a detergent-resistant manner, indicating that it is an integral component of flagella. MNS1–deficient males are sterile, as they exhibit a sharp reduction in sperm production and the remnant sperm are immotile with abnormal short tails. In MNS1–deficient sperm flagella, the characteristic arrangement of “9+2” microtubules and outer dense fibers are completely disrupted. In addition, MNS1–deficient mice display situs inversus and hydrocephalus. MNS1–deficient tracheal motile cilia lack some outer dynein arms in the axoneme. Moreover, MNS1 monomers interact with each other and are able to form polymers in cultured somatic cells. These results demonstrate that MNS1 is essential for spermiogenesis, the assembly of sperm flagella, and motile ciliary functions