A comprehensive ovine model of blood transfusion

Background: The growing awareness of transfusion-associated morbidity and mortality necessitates investigations into the underlying mechanisms. Small animals have been the dominant transfusion model but have associated limitations. This study aimed to develop a comprehensive large animal (ovine) model of transfusion encompassing: blood collection, processing and storage, compatibility testing right through to post-transfusion outcomes. Materials and methods: Two units of blood were collected from each of 12 adult male Merino sheep and processed into 24 ovine-packed red blood cell (PRBC) units. Baseline haematological parameters of ovine blood and PRBC cells were analysed. Biochemical changes in ovine PRBCs were characterized during the 42-day storage period. Immunological compatibility of the blood was confirmed with sera from potential recipient sheep, using a saline and albumin agglutination cross-match. Following confirmation of compatibility, each recipient sheep (n = 12) was transfused with two units of ovine PRBC. Results: Procedures for collecting, processing, cross-matching and transfusing ovine blood were established. Although ovine red blood cells are smaller and higher in number, their mean cell haemoglobin concentration is similar to human red blood cells. Ovine PRBC showed improved storage properties in saline-adenine-glucose-mannitol (SAG-M) compared with previous human PRBC studies. Seventy-six compatibility tests were performed and 17·1% were incompatible. Only cross-match compatible ovine PRBC were transfused and no adverse reactions were observed. Conclusion: These findings demonstrate the utility of the ovine model for future blood transfusion studies and highlight the importance of compatibility testing in animal models involving homologous transfusions

Spin Gaps and Bilayer Coupling in YBa2_2Cu3_3O7−δ_{7-\delta} and YBa2_2Cu4_4O8_8

We investigate the relevance to the physics of underdoped YBa$_2$Cu$_3$O$_{\rm 6+x}$ and YBa$_2$Cu$_4$O$_8$ of the quantum critical point which occurs in a model of two antiferromagnetically coupled planes of antiferromagnetically correlated spins. We use a Schwinger boson mean field theory and a scaling analysis to obtain the phase diagram of the model and the temperature and frequency dependence of various susceptibilities and relaxation rates. We distinguish between a low $\omega ,T$ coupled-planes regime in which the optic spin excitations are frozen out and a high $\omega ,T$ decoupled-planes regime in which the two planes fluctuate independently. In the coupled-planes regime the yttrium nuclear relaxation rate at low temperatures is larger relative to the copper and oxygen rates than would be naively expected in a model of uncorrelated planes. Available data suggest that in YBa$_2$Cu$_4$O$_8$ the crossover from the coupled to the decoupled planes regime occurs at $T 700K$ or $T \sim 200K$. The predicted correlation length is of order 6 lattice constants at $T=200K$. Experimental data related to the antiferromagnetic susceptibility of YBa$_2$Cu$_4$O$_8$ may be made consistent with the theory, but available data for the uniform susceptibility are inconsistent with the theory.Comment: RevTex 3.

Mutation at the Evi1 locus in Junbo mice causes susceptibility to otitis media

Otitis media ( OM), inflammation of the middle ear, remains the most common cause of hearing impairment in children. It is also the most common cause of surgery in children in the developed world. There is evidence from studies of the human population and mouse models that there is a significant genetic component predisposing to OM, yet nothing is known about the underlying genetic pathways involved in humans. We identified an N-ethyl-N-nitrosourea-induced dominant mouse mutant Junbo with hearing loss due to chronic suppurative OM and otorrhea. This develops from acute OM that arises spontaneously in the postnatal period, with the age of onset and early severity dependent on the microbiological status of the mice and their air quality. We have identified the causal mutation, a missense change in the C-terminal zinc finger region of the transcription factor Evi1. This protein is expressed in middle ear basal epithelial cells, fibroblasts, and neutrophil leukocytes at postnatal day 13 and 21 when inflammatory changes are underway. The identification and characterization of the Junbo mutant elaborates a novel role for Evi1 in mammalian disease and implicates a new pathway in genetic predisposition to OM

Agreement among Health Care Professionals in Diagnosing Case Vignette-Based Surgical Site Infections

OBJECTIVE: To assess agreement in diagnosing surgical site infection (SSI) among healthcare professionals involved in SSI surveillance. METHODS: Case-vignette study done in 2009 in 140 healthcare professionals from seven specialties (20 in each specialty, Anesthesiologists, Surgeons, Public health specialists, Infection control physicians, Infection control nurses, Infectious diseases specialists, Microbiologists) in 29 University and 36 non-University hospitals in France. We developed 40 case-vignettes based on cardiac and gastrointestinal surgery patients with suspected SSI. Each participant scored six randomly assigned case-vignettes before and after reading the SSI definition on an online secure relational database. The intraclass correlation coefficient (ICC) was used to assess agreement regarding SSI diagnosis on a seven-point Likert scale and the kappa coefficient to assess agreement for superficial or deep SSI on a three-point scale. RESULTS: Based on a consensus, SSI was present in 21 of 40 vignettes (52.5%). Intraspecialty agreement for SSI diagnosis ranged across specialties from 0.15 (95% confidence interval, 0.00-0.59) (anesthesiologists and infection control nurses) to 0.73 (0.32-0.90) (infectious diseases specialists). Reading the SSI definition improved agreement in the specialties with poor initial agreement. Intraspecialty agreement for superficial or deep SSI ranged from 0.10 (-0.19-0.38) to 0.54 (0.25-0.83) (surgeons) and increased after reading the SSI definition only among the infection control nurses from 0.10 (-0.19-0.38) to 0.41 (-0.09-0.72). Interspecialty agreement for SSI diagnosis was 0.36 (0.22-0.54) and increased to 0.47 (0.31-0.64) after reading the SSI definition. CONCLUSION: Among healthcare professionals evaluating case-vignettes for possible surgical site infection, there was large disagreement in diagnosis that varied both between and within specialties

Life Cycle-Dependent Cytoskeletal Modifications in Plasmodium falciparum Infected Erythrocytes

10.1371/journal.pone.0061170PLoS ONE84

PRIMO: an interactive homology modeling pipeline

The development of automated servers to predict the three-dimensional structure of proteins has seen much progress over the years. These servers make calculations simpler, but largely exclude users from the process. In this study, we present the PRotein Interactive MOdeling (PRIMO) pipeline for homology modeling of protein monomers. The pipeline eases the multi-step modeling process, and reduces the workload required by the user, while still allowing engagement from the user during every step. Default parameters are given for each step, which can either be modified or supplemented with additional external input. PRIMO has been designed for users of varying levels of experience with homology modeling. The pipeline incorporates a user-friendly interface that makes it easy to alter parameters used during modeling

Melatonin protects rats from radiotherapy-induced small intestine toxicity

Radiotherapy-induced gut toxicity is among the most prevalent dose-limiting toxicities following radiotherapy. Prevention of radiation enteropathy requires protection of the small intestine. However, despite the prevalence and burden of this pathology, there are currently no effective treatments for radiotherapy-induced gut toxicity, and this pathology remains unclear. The present study aimed to investigate the changes induced in the rat small intestine after external irradiation of the tongue, and to explore the potential radio-protective effects of melatonin gel. Male Wistar rats were subjected to irradiation of their tongues with an X-Ray YXLON Y.Tu 320-D03 irradiator, receiving a dose of 7.5 Gy/day for 5 days. For 21 days post-irradiation, rats were treated with 45 mg/day melatonin gel or vehicle, by local application into their mouths. Our results showed that mitochondrial oxidative stress, bioenergetic impairment, and subsequent NLRP3 inflammasome activation were involved in the development of radiotherapy-induced gut toxicity. Oral treatment with melatonin gel had a protective effect in the small intestine, which was associated with mitochondrial protection and, consequently, with a reduced inflammatory response, blunting the NF-κB/NLRP3 inflammasome signaling activation. Thus, rats treated with melatonin gel showed reduced intestinal apoptosis, relieving mucosal dysfunction and facilitating intestinal mucosa recovery. Our findings suggest that oral treatment with melatonin gel may be a potential preventive therapy for radiotherapy-induced gut toxicity in cancer patients.This study was partially supported by grant no. SAF2009-14037 from the Spanish Ministry of Economy and Competitivity (MINECO), GREIB.PT_2010_04 from the CEIBiotic Program of the University of Granada, Spain, and CTS-101 from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain

Comparative genetic analysis: the utility of mouse genetic systems for studying human monogenic disease

One of the long-term goals of mutagenesis programs in the mouse has been to generate mutant lines to facilitate the functional study of every mammalian gene. With a combination of complementary genetic approaches and advances in technology, this aim is slowly becoming a reality. One of the most important features of this strategy is the ability to identify and compare a number of mutations in the same gene, an allelic series. With the advent of gene-driven screening of mutant archives, the search for a specific series of interest is now a practical option. This review focuses on the analysis of multiple mutations from chemical mutagenesis projects in a wide variety of genes and the valuable functional information that has been obtained from these studies. Although gene knockouts and transgenics will continue to be an important resource to ascertain gene function, with a significant proportion of human diseases caused by point mutations, identifying an allelic series is becoming an equally efficient route to generating clinically relevant and functionally important mouse models

Comparative Transcriptional and Genomic Analysis of Plasmodium falciparum Field Isolates

Mechanisms for differential regulation of gene expression may underlie much of the phenotypic variation and adaptability of malaria parasites. Here we describe transcriptional variation among culture-adapted field isolates of Plasmodium falciparum, the species responsible for most malarial disease. It was found that genes coding for parasite protein export into the red cell cytosol and onto its surface, and genes coding for sexual stage proteins involved in parasite transmission are up-regulated in field isolates compared with long-term laboratory isolates. Much of this variability was associated with the loss of small or large chromosomal segments, or other forms of gene copy number variation that are prevalent in the P. falciparum genome (copy number variants, CNVs). Expression levels of genes inside these segments were correlated to that of genes outside and adjacent to the segment boundaries, and this association declined with distance from the CNV boundary. This observation could not be explained by copy number variation in these adjacent genes. This suggests a local-acting regulatory role for CNVs in transcription of neighboring genes and helps explain the chromosomal clustering that we observed here. Transcriptional co-regulation of physical clusters of adaptive genes may provide a way for the parasite to readily adapt to its highly heterogeneous and strongly selective environment

Early carboniferous brachiopod faunas from the Baoshan block, west Yunnan, southwest China

38 brachiopod species in 27 genera and subgenera are described from the Yudong Formation in the Shidian-Baoshan area, west Yunnan, southwest China. New taxa include two new subgenera: Unispirifer (Septimispirifer) and Brachythyrina (Longathyrina), and seven new species: Eomarginifera yunnanensis, Marginatia cylindrica, Unispirifer (Unispirifer) xiangshanensis, Unispirifer (Septimispirifer) wafangjieensis, Brachythyrina (Brachythyrina) transversa, Brachythyrina (Longathyrina) baoshanensis, and Girtyella wafangjieensis. Based on the described material and constraints from associated coral and conodont faunas, the age of the brachiopod fauna from the Yudon Formation is considered late Tournaisian (Early Carboniferous), with a possibility extending into earlyViseacutean.<br /