The Density of Knobs on Plasmodium falciparum-Infected Erythrocytes Depends on Developmental Age and Varies among Isolates

Background

The virulence of Plasmodium falciparum malaria is related to the parasite’s ability to evade host immunity through clonal antigenic variation and tissue-specific adhesion of infected erythrocytes (IEs). The P. falciparum erythrocyte membrane protein 1 (PfEMP1) family expressed on dome-shaped protrusions called knobs on the IE surface is central to both. Differences in receptor specificity and affinity of expressed PfEMP1 are important for IE adhesiveness, but it is not known whether differences in the number and size of the knobs on which the PfEMP1 proteins are expressed also play a role. Therefore, the aim of this study was to provide detailed information on isolate- and time-dependent differences in knob size and density.

Methodology/Principal Findings

We used atomic force microscopy to characterize knobs on the surface of P. falciparum-infected erythrocytes. Fourteen ex vivo isolates from Ghanaian children with malaria and 10 P. falciparum isolates selected in vitro for expression of a particular PfEMP1 protein (VAR2CSA) were examined. Knob density increased from ∼20 h to ∼35 h post-invasion, with significant variation among isolates. The knob density ex vivo, which was about five-fold higher than following long-term in vitro culture, started to decline within a few months of culture. Although knob diameter and height varied among isolates, we did not observe significant time-dependent variation in these dimensions.

Conclusions/Significance

The density of knobs on the P. falciparum-IE surface depends on time since invasion, but is also determined by the infecting isolate in a time-independent manner. This is the first study to quantitatively evaluate knob densities and dimensions on different P. falciparum isolates, to examine ex vivo isolates from humans, and to compare ex vivo and long-term in vitro-cultured isolates. Our findings contribute to the understanding of the interaction between P. falciparum parasites and the infected host.     

蜥脚类骨质尾锤之发现

自贡大山铺恐龙化石坑中出土的李氏蜀龙(Shunosaurus lii)和天府峨眉龙(Omeisaurustianfuensis)均发现由尾端脊椎愈合膨大而成之纺锤形骨质尾锤。这一特征在蜥脚类中尚属首次记述。骨质尾锤是一种适应陆地生活之特殊构造。它作为一种防御武器,主要起防卫身体的作用。它的存在说明R.T.Bakker提出的蜥脚类是一类营陆地生活的恐龙的观点是正确的。     

Short-snouted toothless ichthyosaur from China suggests Late Triassic diversification of suction feeding ichthyosaurs

Background

Ichthyosaurs were an important group of Mesozoic marine reptiles and existed from the Early Triassic to the early Late Cretaceous. Despite a great diversity in body shapes and feeding adaptations, all share greatly enlarged eyes, an elongated rostrum with numerous conical teeth, and a streamlined body.

Methodology/Principal Findings

Based on new material from China and the restudy of Shastasaurus pacificus, we here reinterpret the classical large-bodied Late Triassic ichthyosaur genus Shastasaurus to differ greatly from the standard ichthyosaurian body plan, indicating much greater morphological diversity and range of feeding adaptations in ichthyosaurs than previously recognized. Phylogenetic analysis indicates a monophyletic clade consisting of the giant Shonisaurus sikanniensis, Guanlingsaurus liangae, and Shastasaurus pacificus to which the genus name Shastasaurus is applied. Shastasaurus liangae comb. nov. is from the Late Triassic (Carnian) Xiaowa Formation of Guizhou Province, southwestern China. The species combines a diminutive head with an entirely toothless and greatly reduced snout. The species also has by far the highest vertebral count among ichthyosaurs (86 presacral vertebrae and >110 caudal vertebrae), a count that is also very high for tetrapods in general. A reduced toothless snout and a diminutive head is also apparently present in the giant S. sikanniensis and presumably in S. pacificus.

Conclusions/Significance

In analogy to many modern odontocetes, Shastasaurus is interpreted as a specialized suction feeder on unshelled cephalopods and fish, suggesting a unique but widespread Late Triassic diversification of toothless, suction-feeding ichthyosaurs. Suction feeding has not been hypothesized for any of the other diverse marine reptiles of the Mesozoic before, but in Shastasaurus may be linked to the Late Triassic minimum in atmospheric oxygen.     

Mono-allelic retrotransposon insertion addresses epigenetic transcriptional repression in human genome

Background

Retrotransposons have been extensively studied in plants and animals and have been shown to have an impact on human genome dynamics and evolution. Their ability to move within genomes gives retrotransposons to affect genome instability.

Methods

we examined the polymorphic inserted AluYa5, evolutionary young Alu, in the progesterone receptor gene to determine the effects of Alu insertion on molecular environment. We used mono-allelic inserted cell lines which carry both Alu-present and Alu-absent alleles. To determine the epigenetic change and gene expression, we performed restriction enzyme digestion, Pyrosequencing, and Chromatin Immunoprecipitation.

Results

We observed that the polymorphic insertion of evolutionally young Alu causes increasing levels of DNA methylation in the surrounding genomic area and generates inactive histone tail modifications. Consequently the Alu insertion deleteriously inactivates the neighboring gene expression.

Conclusion

The mono-allelic Alu insertion cell line clearly showed that polymorphic inserted repetitive elements cause the inactivation of neighboring gene expression, bringing aberrant epigenetic changes.     

Comparison of Invasive Blood Pressure Measurements from the Caudal Ventral Artery and the Femoral Artery in Male Adult SD and Wistar Rats

Background and Purpose

Studies have suggested that the caudal ventral artery is a potential site for continuous arterial blood pressure monitoring in rats. However, the agreement of mean arterial pressure values between the femoral artery and the caudal ventral artery has not been investigated. This study was performed to identify whether the caudal ventral artery could be safely used for continuous blood pressure monitoring as an alternative site to the femoral artery.

Methods

Rats were randomized into four groups: Sprague Dawley rats under normothermia; Wistar rats under normothermia; Sprague Dawley rats under hypothermia; Wistar rats under hypothermia. Each rat underwent simultaneous monitoring of blood pressure using femoral artery and caudal ventral artery catheterization during a stable hemodynamic state and three periods of acute severe hemodynamic changes. The effects of rat strain, rectal temperature, experimental time course and hemodynamic factors on pressure gradients, the concordance of mean arterial pressure values between the femoral artery and the caudal ventral artery, and the rates of distal ischemia after surgery were determined.

Results

There was a significant difference in the rate of distal ischemia between femoral and caudal ventral arteries after catheterization (25% vs 5%, P<0.05). The overall mean gradient and the mean gradient under a steady hemodynamic state were 4.9±3.7 mm Hg and 5.5±2.5 mm Hg, respectively. The limits of agreement (bias±1.96 SD) were (−2.5 mm Hg, 12.3 mm Hg) and (-0.5 mm Hg, 10.5 mm Hg), respectively. Although the concordance decreased during the first 30 sec of each period of severe hemodynamic changes, the degree of agreement was acceptable regardless of the effects of rat strain and rectal temperature.

Conclusions

Based on the degree of agreement and the safety of catheterization, the caudal ventral artery may be a preferred site for continuous arterial blood pressure monitoring without acute severe hemodynamic changes.     

Gene expression profiles in Rana pirica tadpoles following exposure to a predation threat

Background

Rana pirica tadpoles show morphological changes in response to a predation threat: larvae of the dragonfly Aeshna nigroflava induce heightened tail depth, whereas larval salamander Hynobius retardatus induce a bulgy morphology with heightened tail depth. Although both predators induce similar tail morphologies, it is possible that there are functional differences between these tail morphs.

Results

Here, we performed a discriminant microarray analysis using Xenopus laevis genome arrays to compare tail tissues of control and predator-exposed tadpoles. We identified 9 genes showing large-scale changes in their expression profile: ELAV-like1, methyltransferase like 7A, dolichyl-phosphate mannosyltransferase, laminin subunit beta-1, gremlin 1, BCL6 corepressor-like 1, and three genes of unknown identity. A further 80 genes showed greater than 5 fold differences in expression after exposure to dragonfly larvae and 81 genes showed altered expression after exposure to larval salamanders. Predation-threat responsive genes were identified by selecting genes that reverted to control levels of expression following removal of the predator. Thirteen genes were induced specifically by dragonfly larvae, nine others were salamander-specific, and sixteen were induced by both. Functional analyses indicated that some of the genes induced by dragonfly larvae caused an increase in laminins necessary for cell adhesion in the extracellular matrix. The higher expression of gremlin 1 and HIF1a genes after exposure to dragonfly larvae indicated an in vivo hypoxic reaction, while down-regulation of syndecan-2 may indicate impairment of angiogenesis. Exposure to larval salamanders caused down-regulation of XCIRP-1, which is known to inhibit expression of adhesion molecules; the tadpoles showed reduced expression of cα(E)-catenin, small muscle protein, dystrophin, and myosin light chain genes.

Conclusion

The connective tissue of tadpoles exposed to larval salamanders may be looser. The differences in gene expression profiles induced by the two predators suggest that there are functional differences between the altered tail tissues of the two groups of tadpoles.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1389-4) contains supplementary material, which is available to authorized users.     

DAZL Relieves miRNA-Mediated Repression of Germline mRNAs by Controlling Poly(A) Tail Length in Zebrafish

Background

During zebrafish embryogenesis, microRNA (miRNA) miR-430 contributes to restrict Nanos1 and TDRD7 to primordial germ cells (PGCs) by inducing mRNA deadenylation, mRNA degradation, and translational repression of nanos1 and tdrd7 mRNAs in somatic cells. The nanos1 and tdrd7 3′UTRs include cis-acting elements that allow activity in PGCs even in the presence of miRNA-mediated repression.

Methodology/Principal Findings

Using a GFP reporter mRNA that was fused with tdrd7 3′UTR, we show that a germline-specific RNA-binding protein DAZ-like (DAZL) can relieve the miR-430-mediated repression of tdrd7 mRNA by inducing poly(A) tail elongation (polyadenylation) in zebrafish. We also show that DAZL enhances protein synthesis via the 3′UTR of dazl mRNA, another germline mRNA targeted by miR-430.

Conclusions/Significance

Our present study indicated that DAZL acts as an “anti-miRNA factor” during vertebrate germ cell development. Our data also suggested that miRNA-mediated regulation can be modulated on specific target mRNAs through the poly(A) tail control.     

Transforaminal Decompression and Interbody Fusion in the Treatment of Thoracolumbar Fracture and Dislocation with Spinal Cord Injury

Study Design

A retrospective clinical study.

Objective

To evaluate the efficacy and safety of transforaminal decompression and interbody fusion in the treatment of thoracolumbar fracture and dislocation with spinal cord injury.

Methods

Twenty-six spinal cord injured patients with thoracolumbar fracture and dislocation were treated by transforaminal decompression and interbody fusion. The operation time, intraoperative blood loss, and complications were recorded; the Cobb angle and compressive rate (CR) of the anterior height of two adjacent vertebrae were measured; and the nerve injury was assessed according to sensory scores and motor scores of the American Spinal Injury Association (ASIA) standards for neurological classification of spinal cord injury.

Results

The operative time was 250±57 min, and intraoperative blood loss was 440±168 ml. Cerebrospinal leakage was detected and repaired during the operation in two patients. A total of 24 of 26 patients were followed up for more than 2 years. ASIA sensory scores and motor scores were improved significantly at 3 months and 6 months after operation; the Cobb angle and CR of the anterior height of two adjacent vertebrae were corrected and showed a significant difference at post-operation; and the values were maintained at 3 months after operation and the last follow-up.

Conclusion

We showed that transforaminal decompression together with interbody fusion is an alternative method to treat thoracolumbar fracture and dislocation.     

Martharaptor greenriverensis, a New Theropod Dinosaur from the Lower Cretaceous of Utah

Background

The Yellow Cat Member of the Cedar Mountain Formation (Early Cretaceous, Barremian?) of Utah has yielded a rich dinosaur fauna, including the basal therizinosauroid theropod Falcarius utahensis at its base. Recent excavation uncovered a new possible therizinosauroid taxon from a higher stratigraphic level in the Cedar Mountain Formation than F. utahensis.

Methodology/Principal Findings

Here we describe a fragmentary skeleton of the new theropod and perform a phylogenetic analysis to determine its phylogenetic position. The skeleton includes fragments of vertebrae, a scapula, forelimb and hindlimb bones, and an ischium. It also includes several well-preserved manual unguals. Manual and pedal morphology show that the specimen is distinct from other theropods from the Cedar Mountain Formation and from previously described therizinosauroids. It is here named as the holotype of a new genus and species, Martharaptor greenriverensis. Phylogenetic analysis places M. greenriverensis within Therizinosauroidea as the sister taxon to Alxasaurus + Therizinosauridae, although support for this placement is weak.

Conclusions/Significance

The new specimen adds to the known dinosaurian fauna of the Yellow Cat Member of the Cedar Mountain Formation. If the phylogenetic placement is correct, it also adds to the known diversity of Therizinosauroidea.     

Dopamine Reduction in the Substantia Nigra of Parkinson's Disease Patients Confirmed by In Vivo Magnetic Resonance Spectroscopic Imaging

Objectives

Metabolic changes in the substantia nigra of patients with Parkinson''s disease were previously investigated in different molecular-pathological examinations. The aim of our study was the in vivo measurement of these alterations using three-dimensional magnetic resonance spectroscopic imaging.

Methods

21 patients with Parkinson''s disease and 24 controls were examined using magnetic resonance spectroscopic imaging at 3 Tesla. The spectra of rostral and caudal substantia nigra regions were analyzed using LCModel. For spectral fitting, an adjusted basis data set with pathology-specific metabolites and macromolecules was used to better reproduce the in vivo spectra. To assess differences between both groups more accurately, especially in metabolites at lower concentrations, group-averaged spectra were evaluated in addition to the analysis of individual data.

Results

We found significantly decreased N-acetylaspartate, choline, creatine, myo-inositol, glutathione and dopamine concentrations in patients with Parkinson''s disease compared to controls, whereas glutamine+glutamate, γ-aminobutyric acid, and homovanillic acid were slightly increased. According to anatomical features, clear differences in the biochemical profiles were found between rostral and caudal substantia nigra voxels in both groups.

Conclusions

Reduced N-acetylaspartate and dopamine concentrations result from progressive degeneration of dopamine-producing neurons within the substantia nigra pars compacta. Decreased creatine levels can be interpreted as impaired energy metabolism due to mitochondrial dysfunction. Lower glutathione concentrations might be a cause or consequence of oxidative stress. Furthermore, slightly increased glutamine+glutamate and γ-aminobutyric acid levels are expected based on post mortem data in Parkinson''s disease. To the best of our knowledge, this is the first non-invasive confirmation of these metabolic changes.     

A subadult specimen of Rubeosaurus ovatus (Dinosauria: Ceratopsidae), with observations on other ceratopsids from the two medicine formation

Background

Centrosaurine ceratopsids are well known from the middle Campanian Upper Two Medicine Formation of Montana. Four taxa have been named: Brachyceratops montanensis, Rubeosaurus ovatus, Einiosaurus procurvicornis, and Achelousaurus horneri. Rubeosaurus has been historically the most enigmatic of these taxa; only two specimens, the holotype caudal parietal bar and a referred incomplete skull, have been assigned to Rubeosaurus.

Methodology/Principal Findings

A revised interpretation of the parietal processes of USNM 14765, the partial skeleton of a subadult centrosaurine formerly referred to Brachyceratops, indicates that it shares a P5 spike with the holotype of Rubeosaurus ovatus and should therefore be referred to that taxon. Brachyceratops is considered a nomen dubium.

Conclusions/Significance

USNM 14765 provides additional anatomical information for Rubeosaurus ovatus. These new data are incorporated into a recent phylogenetic analysis of centrosaurine relationships; Rubeosaurus appears as the sister taxon of a clade composed of Einiosaurus, Achelousaurus, and Pachyrhinosaurus.     

A new non-pterodactyloid pterosaur from the Late Jurassic of southern Germany

Background

The ‘Solnhofen Limestone’ beds of the Southern Franconian Alb, Bavaria, southern Germany, have for centuries yielded important pterosaur specimens, most notably of the genera Pterodactylus and Rhamphorhynchus. Here we describe a new genus of non-pterodactyloid pterosaur based on an extremely well preserved fossil of a young juvenile: Bellubrunnus rothgaengeri (gen. et sp. nov.).

Methodology/Principal Findings

The specimen was examined firsthand by all authors. Additional investigation and photography under UV light to reveal details of the bones not easily seen under normal lighting regimes was completed.

Conclusions/Significance

This taxon heralds from a newly explored locality that is older than the classic Solnhofen beds. While similar to Rhamphorhynchus, the new taxon differs in the number of teeth, shape of the humerus and femur, and limb proportions. Unlike other derived non-pterodacytyloids, Bellubrunnus lacks elongate chevrons and zygapophyses in the tail, and unlike all other known pterosaurs, the wingtips are curved anteriorly, potentially giving it a unique flight profile.     

Fli+ etsrp+ hemato-vascular progenitor cells proliferate at the lateral plate mesoderm during vasculogenesis in zebrafish

Background

Vasculogenesis, the de novo formation of blood vessels from precursor cells is critical for a developing embryo. However, the signals and events that dictate the formation of primary axial vessels remain poorly understood.

Methodology/Principal Findings

In this study, we use ets-related protein-1 (etsrp), which is essential for vascular development, to analyze the early stages of vasculogenesis in zebrafish. We found etsrp ⁺ cells of the head, trunk and tail follow distinct developmental sequences. Using a combination of genetic, molecular and chemical approaches, we demonstrate that fli ⁺ etsrp ⁺ hemato-vascular progenitors (FEVPs) are proliferating at the lateral plate mesoderm (LPM). The Shh-VEGF-Notch-Hey2 signaling pathway controls the proliferation process, and experimental modulation of single components of this pathway alters etsrp ⁺ cell numbers at the LPM.

Conclusions/Significance

This study for the first time defines factors controlling proliferation, and cell numbers of pre-migratory FEVPs in zebrafish.     

Modeling the spread of vector-borne diseases on bipartite networks

Background

Vector-borne diseases for which transmission occurs exclusively between vectors and hosts can be modeled as spreading on a bipartite network.

Methodology/Principal Findings

In such models the spreading of the disease strongly depends on the degree distribution of the two classes of nodes. It is sufficient for one of the classes to have a scale-free degree distribution with a slow enough decay for the network to have asymptotically vanishing epidemic threshold. Data on the distribution of Ixodes ricinus ticks on mice and lizards from two independent studies are well described by a scale-free distribution compatible with an asymptotically vanishing epidemic threshold. The commonly used negative binomial, instead, cannot describe the right tail of the empirical distribution.

Conclusions/Significance

The extreme aggregation of vectors on hosts, described by the power-law decay of the degree distribution, makes the epidemic threshold decrease with the size of the network and vanish asymptotically.