Chromosomal-level assembly of the Asian Seabass genome using long sequence reads and multi-layered scaffolding

We report here the ~670 Mb genome assembly of the Asian seabass (Lates calcarifer), a tropical marine teleost. We used long-read sequencing augmented by transcriptomics, optical and genetic mapping along with shared synteny from closely related fish species to derive a chromosome-level assembly with a contig N50 size over 1 Mb and scaffold N50 size over 25 Mb that span ~90% of the genome. The population structure of L. calcarifer species complex was analyzed by re-sequencing 61 individuals representing various regions across the species' native range. SNP analyses identified high levels of genetic diversity and confirmed earlier indications of a population stratification comprising three clades with signs of admixture apparent in the South-East Asian population. The quality of the Asian seabass genome assembly far exceeds that of any other fish species, and will serve as a new standard for fish genomics

Ultrafast 3d spin-echo acquisition improves gadolinium-enhanced mri signal contrast enhancement

Long scan times of 3D volumetric MR acquisitions usually necessitate ultrafast in vivo gradient-echo acquisitions, which are intrinsically susceptible to magnetic field inhomogeneities. This is especially problematic for contrast-enhanced (CE)-MRI applications, where non-negligible T 2 & z.ast; effect of contrast agent deteriorates the positive signal contrast and limits the available range of MR acquisition parameters and injection doses. To overcome these shortcomings without degrading temporal resolution, ultrafast spin-echo acquisitions were implemented. Specifically, a multiplicative acceleration factor from multiple spin echoes (??32) and compressed sensing (CS) sampling (??8) allowed highly-accelerated 3D Multiple-Modulation- Multiple-Echo (MMME) acquisition. At the same time, the CE-MRI of kidney with Gd-DOTA showed significantly improved signal enhancement for CS-MMME acquisitions (??7) over that of corresponding FLASH acquisitions (??2). Increased positive contrast enhancement and highly accelerated acquisition of extended volume with reduced RF irradiations will be beneficial for oncological and nephrological applications, in which the accurate in vivo 3D quantification of contrast agent concentration is necessary with high temporal resolution.open0

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects. Accordingly, the search for new therapeutic methods constitutes an active investigation field. The use of mesenchymal stem cells (MSCs) to modify the disease course is currently the subject of intense interest. Decidua-derived MSCs (DMSCs) are a cell population obtained from human placental extraembryonic membranes able to differentiate into the three germ layers. This study explores the therapeutic potential of DMSCs. Methods: We used the experimental autoimmune encephalomyelitis (EAE) animal model to evaluate the effect of DMSCs on clinical signs of the disease and on the presence of inflammatory infiltrates in the central nervous system. We also compared the inflammatory profile of spleen T cells from DMSC-treated mice with that of EAE control animals, and the influence of DMSCs on the in vitro definition of the Th17 phenotype. Furthermore, we analyzed the effects on the presence of some critical cell types in central nervous system infiltrates. Results: Preventive intraperitoneal injection of DMSCs resulted in a significant delay of external signs of EAE. In addition, treatment of animals already presenting with moderate symptoms resulted in mild EAE with reduced disease scores. Besides decreased inflammatory infiltration, diminished percentages of CD4+IL17+, CD11b+Ly6G+ and CD11b+Ly6C+ cells were found in infiltrates of treated animals. Early immune response was mitigated, with spleen cells of DMSC-treated mice displaying low proliferative response to antigen, decreased production of interleukin (IL)-17, and increased production of the anti-inflammatory cytokines IL-4 and IL-10. Moreover, lower RORγT and higher GATA-3 expression levels were detected in DMSC-treated mice. DMSCs also showed a detrimental influence on the in vitro definition of the Th17 phenotype. Conclusions: DMSCs modulated the clinical course of EAE, modified the frequency and cell composition of the central nervous system infiltrates during the disease, and mediated an impairment of Th17 phenotype establishment in favor of the Th2 subtype. These results suggest that DMSCs might provide a new cell-based therapy for the control of multiple sclerosis.This work was sponsored by grants from Acción Estratégica en Salud (PI13/00297 and PI11/00581), the Neurosciences and Aging Foundation, the Francisco Soria Melguizo Foundation, Octopharma, and Parkinson Madrid (PI2012/0032).S

More stories on Th17 cells

For more than two decades, immunologists have been using the so-called Th1/Th2 paradigm to explain most of the phenomena related to adaptive immunity. the Th1/Th2 paradigm implied the existence of two different, mutually regulated, CD4(+) T helper subsets: Th1 cells, driving cell-mediated immune responses involved in tissue damage and fighting infection against intracellular parasites; and Th2 cells that mediate IgE production and are particularly involved in eosinophilic inflammation, allergy and clearance of helminthic infections. A third member of the T helper set, IL-17-producing CD4(+) T cells, now called Th17 cells, was recently described as a distinct lineage that does not share developmental pathways with either Th1 or Th2 cells. the Th17 subset has been linked to autoimmune disorders, being able to produce IL-17, IL-17F and IL-21 among other inflammatory cytokines. Interestingly, it has been reported that there is not only a cross-regulation among Th1, Th2 and Th17 effector cells but there is also a dichotomy in the generation of Th17 and T regulatory cells. Therefore, Treg and Th17 effector cells arise in a mutually exclusive fashion, depending on whether they are activated in the presence of TGF-beta or TGF-beta plus inflammatory cytokines such as IL-6. This review will address the discovery of the Th17 cells, and recent progress on their development and regulation.Crohn's and Colitis Foundation of AmericaNIHLa Jolla Inst Allergy & Immunol, La Jolla, CA 92037 USAUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Microbiol Immunol & Parasitol, São Paulo, BrazilNIH: RO1 AI050265-06Web of Scienc

Study of Radiologic Technologists’ Perceptions of Picture Archiving and Communication System (PACS) Competence and Educational Issues in Western Australia

Although the implementation of picture archiving and communication system (PACS) could increase productivity of radiology departments, this depends on factors such as the PACS competence of radiologic technologists (RTs). The purpose of this study was to investigate the RTs’ perceptions of PACS competence and educational issues in Western Australia (WA). A hardcopy questionnaire was distributed to WA RTs for obtaining their perceptions of PACS competence and educational issues. Descriptive (percentage of frequency, mean and standard deviation) and inferential statistics (t test and analysis of variance) were used to analyze the responses of the multiple choice and five-point scale questions from the returned questionnaires. The questionnaire response rate was 57.7 % (173 out of 300). The mean values of all PACS competence questions except questions 2e–g are in the range of 3.9–4.9, i.e., around competent to very competent. Participants indicated they received adequate PACS training (mean 3.8). Statistically significant variables influencing RTs’ perceptions of their PACS competence and educational issues including the age (p < 0.01), gender (p < 0.05), years of practice (p < 0.005–0.05), primary duty (p < 0.05), medical imaging qualification (p < 0.001), general computer skills (p < 0.001), and type of PACS education received (p < 0.001–0.05). The WA RTs indicated that they were competent in using the modality workstation, PACS and radiology information system, and received adequate training. However, future PACS education programs should be tailored to different RTs’ groups. For example, multiple training modules might be necessary to support the PACS competence development of older RTs and those with lower general computer literacy

Genome-wide association and functional follow-up reveals new loci for kidney function

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD

Prospective Volumetric Assessment of the Liver on a Personal Computer by Nonradiologists Prior to Partial Hepatectomy

Ó The Author(s) 2010. This article is published with open access at Springerlink.com Background A small remnant liver volume is an important risk factor for posthepatectomy liver failure. ImageJ and OsiriX Ò are both free, open-source image processing software packages. The aim of the present study was to compare ImageJ and OsiriX Ò in performing prospective computed tomography (CT) volumetric analysis of the liver on a personal computer (PC) in patients undergoing major liver resection. Methods Patients scheduled for a right hemihepatectomy were eligible for inclusion. Two surgeons and one surgical trainee measured volumes of total liver, tumor, and future resection specimen prospectively with ImageJ and OsiriX Ò. A radiologist also measured these volumes with CT scanner-linked Aquarius iNtuition Ò software. Resection volumes were compared with the actual weights of the live

A Genomic-Based Approach Combining In Vivo Selection in Mice to Identify a Novel Virulence Gene in Leishmania

Parasites of the genus Leishmania cause a variety of human diseases that range from destructive skin lesions caused by L. major to visceral infections of the liver and spleen caused by L. donovani that result in death. The Leishmania genes responsible for these different pathologies are not known. In the present study, we used a comparative genome-based approach to introduce and over-express L. donovani genes in L. major to determine whether this results in increased virulence of L. major in visceral organs of infected mice. Through this approach, a novel gene termed Li1040 was identified that is potentially involved in protein transport and was shown to increase pathogenesis in the visceral organs in mice. The Li1040 gene may therefore represent a Leishmania virulence gene that has the potential to regulate the pathology of infection in the mammalian host. These observations help to define how Leishmania causes fatal infections in humans and therefore provide a parasite-specific target for therapy

Common Variants in CRP and LEPR Influence High Sensitivity C-Reactive Protein Levels in North Indians

BACKGROUND: High sensitivity C-reactive protein (hsCRP) levels are shown to be influenced by genetic variants in Europeans; however, little is explored in Indian population. METHODS: Herein, we comprehensively evaluated association of all previously reported genetic determinants of hsCRP levels, including 18 cis (proximal to CRP gene) and 73 trans-acting (distal to CRP gene) variants in 4,200 North Indians of Indo-European ethnicity. First, we evaluated association of 91 variants from 12 candidate loci with hsCRP levels in 2,115 North Indians (1,042 non-diabetic subjects and 1,073 patients with type 2 diabetes). Then, cis and trans-acting variants contributing maximally to hsCRP level variation were further replicated in an independent 2,085 North Indians (1,047 patients with type 2 diabetes and 1,038 non-diabetic subjects). RESULTS: We found association of 12 variants from CRP, LEPR, IL1A, IL6, and IL6R with hsCRP levels in non-diabetic subjects. However, only rs3093059-CRP [β = 0.33, P = 9.6×10⁻⁵] and the haplotype harboring rs3093059 risk allele [β = 0.32 µg/mL, P = 1.4×10⁻⁴/P(perm) = 9.0×10⁻⁴] retained significance after correcting for multiple testing. The cis-acting variant rs3093059-CRP had maximum contribution to the variance in hsCRP levels (1.14%). Among, trans-acting variants, rs1892534-LEPR was observed to contribute maximally to hsCRP level variance (0.59%). Associations of rs3093059-CRP and rs1892534-LEPR were confirmed by replication and attained higher significance after meta-analysis [β(meta) = 0.26/0.22; P(meta) = 4.3×10⁻⁷/7.4×10⁻³ and β(meta) = -0.15/-0.12; P(meta) = 2.0×10⁻⁶/1.6×10⁻⁶ for rs3093059 and rs1892534, respectively in non-diabetic subjects and all subjects taken together]. CONCLUSION: In conclusion, we identified rs3093059 in CRP and rs1892534 in LEPR as major cis and trans-acting contributor respectively, to the variance in hsCRP levels in North Indian population

Sleeping with the Enemy: How Intracellular Pathogens Cope with a Macrophage Lifestyle

Sleeping with the Enemy: How Intracellular Pathogens Cope with a Macrophage Lifestyl