Exploring the Transcriptomic Data of the Australian Paralysis Tick, Ixodes Holocyclus

Ixodes holocyclus is the paralysis tickcommonly found in Australia. I. holocyclus does notcause paralysis in the primary host – bandicoots, butmarkedly affects secondary hosts such as companionanimals, livestock and humans. Holocyclotoxins are theneurotoxin molecules in I. holocyclus responsible forparalysis symptoms. There is a limited understanding ofholocyclotoxins due to the difficulties in purifying andexpressing these toxins in vitro. Next-generationsequencing technologies were utilised for the first time togenerate transcriptome data from two cDNA samples –salivary glands samples collected from female adult ticksengorged on paralysed companion animals and onbandicoots. Contig-encoded proteins in each librarywere annotated according to their best BLAST matchagainst several databases and functionally assigned intosix protein categories: housekeeping, transposableelements, pathogen-related, hypothetical, secreted andnovel. The “secreted protein” category is comprised often protein families: enzymes, protease inhibitors,antigens, mucins, immunity-related, lipocalins, glycinerich,putative secreted, salivary and toxin-like.Comparisons of contig representation between the twolibraries reveal the differential expression of tickproteins collected from different hosts. This studyprovides a preliminary description of the I. holocyclustick salivary gland transcriptome

Efficacy of prenatal ultrasonography in diagnosing urogenital developmental anomalies in newborns.

BACKGROUND: Showing a prevalence rate of 0.5-0.8%, urogenital malformations discovered in newborns is regarded relatively common. The aim of this study is to examine the efficacy of ultrasound diagnostics in detecting developmental disorders in the urogenital system. METHODS: We have processed the prenatal sonographic and postnatal clinical details of 175 urogenital abnormalities in 140 newborns delivered with urogenital malformation according to EUROCAT recommendations over a 5-year period between 2006 and 2010. The patients were divided into three groups; Group 1: prenatal sonography and postnatal examinations yielded fully identical results. Group 2: postnatally detected urogenital changes were partially discovered in prenatal investigations. Group 3: prenatal sonography failed to detect the urogenital malformation identified in postnatal examinations. Urogenital changes representing part of certain multiple disorders associated with chromosomal aberration were investigated separately. RESULTS: Prenatal sonographic diagnosis and postnatal results completely coincided in 45%, i.e. 63/140 of cases in newborns delivered with urogenital developmental disorders. In 34/140 cases (24%), discovery was partial, while in 43/140 patients (31%), no urogenital malformation was detected prenatally. No associated malformations were observed in 108 cases, in 57 of which (53%), the results of prenatal ultrasonography and postnatal examinations showed complete coincidence. Prenatally, urogenital changes were found in 11 patients (10%), whereas no urogenital disorders were diagnosed in 40 cases (37%) by investigations prior to birth. Urogenital disorders were found to represent part of multiple malformations in a total of 28 cases as follows: prenatal diagnosis of urogenital malformation and the findings of postnatal examinations completely coincided in three patients (11%), partial coincidence was found in 22 newborns (79%) and in another three patients (11%), the disorder was not detected prenatally. In four newborns, chromosomal aberration was associated with the urogenital disorder; 45,X karyotype was detected in two patients, trisomy 9 and trisomy 18 were found in one case each. CONCLUSION: In approximately half of the cases, postnatally diagnosed abnormalities coincided with the prenatally discovered fetal urogenital developmental disorders. The results have confirmed that ultrasonography plays an important role in diagnosing urogenital malformations but it fails to detect all of the urogenital developmental abnormalities

Confined dense circumstellar material surrounding a regular type II supernova

With the advent of new wide-field, high-cadence optical transient surveys, our understanding of the diversity of core-collapse supernovae has grown tremendously in the last decade. However, the pre-supernova evolution of massive stars, which sets the physical backdrop to these violent events, is theoretically not well understood and difficult to probe observationally. Here we report the discovery of the supernova iPTF 13dqy = SN 2013fs a mere ∼3 h after explosion. Our rapid follow-up observations, which include multiwavelength photometry and extremely early (beginning at ∼6 h post-explosion) spectra, map the distribution of material in the immediate environment (≲1015 cm) of the exploding star and establish that it was surrounded by circumstellar material (CSM) that was ejected during the final ∼1 yr prior to explosion at a high rate, around 10-3 solar masses per year. The complete disappearance of flash-ionized emission lines within the first several days requires that the dense CSM be confined to within ≲1015 cm, consistent with radio non-detections at 70–100 days. The observations indicate that iPTF 13dqy was a regular type II supernova; thus, the finding that the probable red supergiant progenitor of this common explosion ejected material at a highly elevated rate just prior to its demise suggests that pre-supernova instabilities may be common among exploding massive stars. © 2017 Nature Publishing Grou

Selective Attenuation of Norepinephrine Release and Stress-Induced Heart Rate Increase by Partial Adenosine A1 Agonism

The release of the neurotransmitter norepinephrine (NE) is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR), NE release was induced by electrical stimulation under control conditions (S1), and with capadenoson 6 · 10−8 M (30 µg/l), 6 · 10−7 M (300 µg/l) or 2-chloro-N6-cyclopentyladenosine (CCPA) 10−6 M (S2). Under control conditions (S1), NE release was significantly higher in SHR hearts compared to Wistar (766+/−87 pmol/g vs. 173+/−18 pmol/g, p<0.01). Capadenoson led to a concentration-dependent decrease of the stimulation–induced NE release in SHR (S2/S1 = 0.90±0.08 with capadenoson 6 · 10−8 M, 0.54±0.02 with 6 · 10−7 M), but not in Wistar hearts (S2/S1 = 1.05±0.12 with 6 · 10−8 M, 1.03±0.09 with 6 · 10−7 M). CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/−2% A1-receptor stimulation). These results suggest that partial adenosine A1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release

Experimental Assessment of the Water Quality Influence on the Phosphorus Uptake of an Invasive Aquatic Plant: Biological Responses throughout Its Phenological Stage

International audienceUnderstanding how an invasive plant can colonize a large range of environments is still a great challenge in freshwater ecology. For the first time, we assessed the relative importance of four factors on the phosphorus uptake and growth of an invasive macrophyte Elodea nuttallii (Planch.) St. John. This study provided data on its phenotypic plasticity, which is frequently suggested as an important mechanism but remains poorly investigated. The phosphorus uptake of two Elodea nuttallii subpopulations was experimentally studied under contrasting environmental conditions. Plants were sampled in the Rhine floodplain and in the Northern Vosges mountains, and then maintained in aquaria in hard (Rhine) or soft (Vosges) water. Under these conditions, we tested the influence of two trophic states (eutrophic state, 100 mu g.l(-1) P-PO43- and hypertrophic state, 300 mu g.l(-1) P-PO43-) on the P metabolism of plant subpopulations collected at three seasons (winter, spring and summer). Elodea nuttallii was able to absorb high levels of phosphorus through its shoots and enhance its phosphorus uptake, continually, after an increase of the resource availability (hypertrophic > eutrophic). The lowest efficiency in nutrient use was observed in winter, whereas the highest was recorded in spring, what revealed thus a storage strategy which can be beneficial to new shoots. This experiment provided evidence that generally, the water trophic state is the main factor governing P uptake, and the mineral status (softwater > hardwater) of the stream water is the second main factor. The phenological stage appeared to be a confounding factor to P level in water. Nonetheless, phenology played a role in P turnover in the plant. Finally, phenotypic plasticity allows both subpopulations to adapt to a changing environment

Mutations at the Subunit Interface of Yeast Proliferating Cell Nuclear Antigen Reveal a Versatile Regulatory Domain

Acknowledgments We thank Szilvia Minorits for technical assistance. I.U. conceived and designed the project and wrote the manuscript. All authors participated in designing and performing the experiments, and analyzing the results. The authors declare no competing financial interests. This work was also supported by a grant from the National Research, Development and Innovation Office GINOP-2.3.2-15-2016-00001. Funding: This work was supported by Hungarian Science Foundation Grant OTKA 109521 and National Research Development and Innovation Office GINOP-2.3.2-15-2016-00001. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

Association of circulating calprotectin with lipid profile in axial spondyloarthritis

Calprotectin (CPT) is released during inflammation, also in the context of atherosclerosis. The link between CPT and the atherosclerotic process was evaluated in several diseases. However, studies in axial spondyloarthritis (axSpA), associated with a high incidence of subclinical atherosclerosis, are scarce. Therefore, we assessed the association of CPT with subclinical atherosclerosis and metabolic risk factors in axSpA. CPT serum levels were measured by enzyme-linked immunosorbent assay in 163 axSpA patients and 63 controls. Subclinical atherosclerosis was determined in patients by carotid ultrasonography (assessing the presence/absence of carotid plaques and carotid intima-media thickness [cIMT]). Data on inflammation, disease activity, lipid profile and treatment were collected to evaluate its relationship with CPT. axSpA patients evidenced lower CPT levels than controls. CPT showed no association with plaques or cIMT in axSpA. CPT and HDL-cholesterol negatively correlated, while a positive association of CPT with the atherogenic index was disclosed. Additionally, axSpA patients with C-reactive protein values at diagnosis higher than 3?mg/L displayed higher CPT levels. Our study shows no relationship between CPT and markers of subclinical atherosclerosis in axSpA. Nevertheless, it demonstrates an association of CPT with adverse lipid profiles and inflammatory biomarkers, which could further influence on the development of atherosclerosis.We wish to thank all the patients and controls that participated in this study and Begoña Ubilla for technical assistance. FG is a recipient of a Sara Borrell post-doctoral fellowship from the Instituto de Salud Carlos III (ISCIII) (Spain), co-funded by the European Social Fund (ESF, “Investing in your future”) (grant CD15/00095). SR-M is supported by funds of the RETICS Program (RIER) RD16/0012/0009 (ISCIII, co-funded by the European Regional Development Fund, ERDF). VM is supported by funds of a Miguel Servet type I programme (grant CP16/00033) (ISCIII, co-funded by ERDF). RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, co-funded by the ESF (grant CP16/00033). This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors

Selective Targeting of TRPV1 Expressing Sensory Nerve Terminals in the Spinal Cord for Long Lasting Analgesia

Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX), a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1), causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain

CD152 (CTLA-4) Determines CD4 T Cell Migration In Vitro and In Vivo

BACKGROUND:Migration of antigen-experienced T cells to secondary lymphoid organs and the site of antigenic-challenge is a mandatory prerequisite for the precise functioning of adaptive immune responses. The surface molecule CD152 (CTLA-4) is mostly considered as a negative regulator of T cell activation during immune responses. It is currently unknown whether CD152 can also influence chemokine-driven T cell migration. METHODOLOGY/PRINCIPAL FINDINGS:We analyzed the consequences of CD152 signaling on Th cell migration using chemotaxis assays in vitro and radioactive cell tracking in vivo. We show here that the genetic and serological inactivation of CD152 in Th1 cells reduced migration towards CCL4, CXCL12 and CCL19, but not CXCL9, in a G-protein dependent manner. In addition, retroviral transduction of CD152 cDNA into CD152 negative cells restored Th1 cell migration. Crosslinking of CD152 together with CD3 and CD28 stimulation on activated Th1 cells increased expression of the chemokine receptors CCR5 and CCR7, which in turn enhanced cell migration. Using sensitive liposome technology, we show that mature dendritic cells but not activated B cells were potent at inducing surface CD152 expression and the CD152-mediated migration-enhancing signals. Importantly, migration of CD152 positive Th1 lymphocytes in in vivo experiments increased more than 200% as compared to CD152 negative counterparts showing that indeed CD152 orchestrates specific migration of selected Th1 cells to sites of inflammation and antigenic challenge in vivo. CONCLUSIONS/SIGNIFICANCE:We show here, that CD152 signaling does not just silence cells, but selects individual ones for migration. This novel activity of CD152 adds to the already significant role of CD152 in controlling peripheral immune responses by allowing T cells to localize correctly during infection. It also suggests that interference with CD152 signaling provides a tool for altering the cellular composition at sites of inflammation and antigenic challenge