Sexual Development in Plasmodium: Lessons from Functional Analyses

Malaria is a devastating global disease with several hundred million clinical cases and just under 1 million deaths each yea

ZyFISH: A Simple, Rapid and Reliable Zygosity Assay for Transgenic Mice

Microinjection of DNA constructs into fertilized mouse oocytes typically results in random transgene integration at a single genomic locus. The resulting transgenic founders can be used to establish hemizygous transgenic mouse lines. However, practical and experimental reasons often require that such lines be bred to homozygosity. Transgene zygosity can be determined by progeny testing assays which are expensive and time-consuming, by quantitative Southern blotting which is labor-intensive, or by quantitative PCR (qPCR) which requires transgene-specific design. Here, we describe a zygosity assessment procedure based on fluorescent in situ hybridization (zyFISH). The zyFISH protocol entails the detection of transgenic loci by FISH and the concomitant assignment of homozygosity using a concise and unbiased scoring system. The method requires small volumes of blood, is scalable to at least 40 determinations per assay, and produces results entirely consistent with the progeny testing assay. This combination of reliability, simplicity and cost-effectiveness makes zyFISH a method of choice for transgenic mouse zygosity determinations

Scans for signatures of selection in Russian cattle breed genomes reveal new candidate genes for environmental adaptation and acclimation

Domestication and selective breeding has resulted in over 1000 extant cattle breeds. Many of these breeds do not excel in important traits but are adapted to local environments. These adaptations are a valuable source of genetic material for efforts to improve commercial breeds. As a step toward this goal we identified candidate regions to be under selection in genomes of nine Russian native cattle breeds adapted to survive in harsh climates. After comparing our data to other breeds of European and Asian origins we found known and novel candidate genes that could potentially be related to domestication, economically important traits and environmental adaptations in cattle. The Russian cattle breed genomes contained regions under putative selection with genes that may be related to adaptations to harsh environments (e.g., AQP5, RAD50, and RETREG1). We found genomic signatures of selective sweeps near key genes related to economically important traits, such as the milk production (e.g., DGAT1, ABCG2), growth (e.g., XKR4), and reproduction (e.g., CSF2). Our data point to candidate genes which should be included in future studies attempting to identify genes to improve the extant breeds and facilitate generation of commercial breeds that fit better into the environments of Russia and other countries with similar climates

Joint multi-field T1 quantification for fast field-cycling MRI

Acknowledgment This article is based upon work from COST Action CA15209, supported by COST (European Cooperation in Science and Technology). Oliver Maier is a Recipient of a DOC Fellowship (24966) of the Austrian Academy of Sciences at the Institute of Medical Engineering at TU Graz. The authors would like to acknowledge the NVIDIA Corporation Hardware grant support.Peer reviewedPublisher PD

CRF1-R Activation of the Dynorphin/Kappa Opioid System in the Mouse Basolateral Amygdala Mediates Anxiety-Like Behavior

Stress is a complex human experience and having both rewarding and aversive motivational properties. The adverse effects of stress are well documented, yet many of underlying mechanisms remain unclear and controversial. Here we report that the anxiogenic properties of stress are encoded by the endogenous opioid peptide dynorphin acting in the basolateral amygdala. Using pharmacological and genetic approaches, we found that the anxiogenic-like effects of Corticotropin Releasing Factor (CRF) were triggered by CRF1-R activation of the dynorphin/kappa opioid receptor (KOR) system. Central CRF administration significantly reduced the percent open-arm time in the elevated plus maze (EPM). The reduction in open-arm time was blocked by pretreatment with the KOR antagonist norbinaltorphimine (norBNI), and was not evident in mice lacking the endogenous KOR ligand dynorphin. The CRF1-R agonist stressin 1 also significantly reduced open-arm time in the EPM, and this decrease was blocked by norBNI. In contrast, the selective CRF2-R agonist urocortin III did not affect open arm time, and mice lacking CRF2-R still showed an increase in anxiety-like behavior in response to CRF injection. However, CRF2-R knockout animals did not develop CRF conditioned place aversion, suggesting that CRF1-R activation may mediate anxiety and CRF2-R may encode aversion. Using a phosphoselective antibody (KORp) to identify sites of dynorphin action, we found that CRF increased KORp-immunoreactivity in the basolateral amygdala (BLA) of wildtype, but not in mice pretreated with the selective CRF1-R antagonist, antalarmin. Consistent with the concept that acute stress or CRF injection-induced anxiety was mediated by dynorphin release in the BLA, local injection of norBNI blocked the stress or CRF-induced increase in anxiety-like behavior; whereas norBNI injection in a nearby thalamic nucleus did not. The intersection of stress-induced CRF and the dynorphin/KOR system in the BLA was surprising, and these results suggest that CRF and dynorphin/KOR systems may coordinate stress-induced anxiety behaviors and aversive behaviors via different mechanisms

Amazonian chemical weathering rate derived from stony meteorite finds at Meridiani Planum on Mars

© The Author(s) 2016.Spacecraft exploring Mars such as the Mars Exploration Rovers Spirit and Opportunity, as well as the Mars Science Laboratory or Curiosity rover, have accumulated evidence for wet and habitable conditions on early Mars more than 3 billion years ago. Current conditions, by contrast, are cold, extremely arid and seemingly inhospitable. To evaluate exactly how dry today's environment is, it is important to understand the ongoing current weathering processes. Here we present chemical weathering rates determined for Mars. We use the oxidation of iron in stony meteorites investigated by the Mars Exploration Rover Opportunity at Meridiani Planum. Their maximum exposure age is constrained by the formation of Victoria crater and their minimum age by erosion of the meteorites. The chemical weathering rates thus derived are ~1 to 4 orders of magnitude slower than that of similar meteorites found in Antarctica where the slowest rates are observed on Earth

Author Correction: Abnormal contractility in human heart myofibrils from patients with dilated cardiomyopathy due to mutations in TTN and contractile protein genes

Correction to: Scientific Reportshttps://doi.org/10.1038/s41598-017-13675-8, published online 01 November 201

Should the Arteriovenous Fistula Be Created before Starting Dialysis?: A Decision Analytic Approach

Background: An arteriovenous fistula (AVF) is considered the vascular access of choice, but uncertainty exists about the\ud optimal time for its creation in pre-dialysis patients. The aim of this study was to determine the optimal vascular access\ud referral strategy for stage 4 (glomerular filtration rate ,30 ml/min/1.73 m2) chronic kidney disease patients using a decision\ud analytic framework.\ud Methods: A Markov model was created to compare two strategies: refer all stage 4 chronic kidney disease patients for an\ud AVF versus wait until the patient starts dialysis. Data from published observational studies were used to estimate the\ud probabilities used in the model. A Markov cohort analysis was used to determine the optimal strategy with life expectancy\ud and quality adjusted life expectancy as the outcomes. Sensitivity analyses, including a probabilistic sensitivity analysis, were\ud performed using Monte Carlo simulation.\ud Results: The wait strategy results in a higher life expectancy (66.6 versus 65.9 months) and quality adjusted life expectancy\ud (38.9 versus 38.5 quality adjusted life months) than immediate AVF creation. It was robust across all the parameters except\ud at higher rates of progression and lower rates of ischemic steal syndrome.\ud Conclusions: Early creation of an AVF, as recommended by most guidelines, may not be the preferred strategy in all predialysis\ud patients. Further research on cost implications and patient preferences for treatment options needs to be done\ud before recommending early AVF creation