The influence of poly (2-methoxyaniline-5-sulfonic acid) on the electrochemical and photochemical properties of a highly luminescent ruthenium complex

Immobilisation of a luminescent material on an electrode surface is well known to substantially modulate its photophysical and electrochemical properties. Here a positively charged ruthenium metal complex ([Ru(bpy)(3)](2+)) is immobilised on all electrode surface by ion paring with a sulfonated conducting polymer poly(2-methoxyaniline-5-sulfonic acid), (PMAS). Significantly, our study reveals that the electron transport between the ruthenium metal centres can be greatly enhanced due to the interaction with the conducting polymer when both are surface confined. Charge transfer diffusion rates in the present system are an order of magnitude faster than those found where the metal centre is immobilised within a non-conducting polymeric matrix. Electron transport appears to be mediated through the PMAS conjugated structure, contrasting with the electron hopping process typically observed in non-conducting metallopolymers. This increased regeneration rate causes the ruthenium-based electrochemiluminescence (ECL) efficiency to be increased. The impact of these observations on the ECL detection of low concentrations of disease biomarkers is discussed. (c) 2007 Published by Elsevier Ltd

Assessing the Efficacy of Ventilation of Anesthetized Neonatal Calves Using a Laryngeal Mask Airway or Mask Resuscitator

Calves that have undergone a dystocia are often hypoxic and acidemic, which can result in reduced vigor and subsequent mortality. Methods of field resuscitation of apneic newborn calves are often ineffective and therefore underutilized. This proof-of-concept study aimed to determine the efficacy of the laryngeal mask airway (LMA) as well as the current industry standard method of ventilation, the McCulloch Calf Aspirator/ Resuscitator (MMR) for positive pressure ventilation of neonatal calves. Five LMA models of various sizes were first tested in cadaver heads to assess anatomical fit. Three LMA models in two sizes each were then tested in two anesthetized calves to determine the model best suited to ventilate calves. Next, the selected LMA and the MMR were both assessed for efficacy of ventilation. Six anesthetized calves had hypoventilation induced by administering alfaxalone intravenously. Calves were ventilated for 3 min with the LMA, allowed a brief washout period, then given a second administration of alfaxalone prior to ventilation with the MMR. Serial arterial blood gas analyses were performed prior to ventilation (baseline), at 1, 2, and 3 min during ventilation, and 1 min after ventilation had ceased. Success of ventilation was assessed by monitoring partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), bicarbonate (HCO3-), pH, L-lactate, and hemoglobin saturation (SaO2) in arterial blood. A one-way ANOVA for repeated measures with Bonferroni correction was used to assess the efficacy of ventilation of each device compared to baseline. For the LMA, PaO2, SaO2, and pH were significantly higher than baseline throughout ventilation and PaCO2 was significantly lower than baseline at 1 min of ventilation. For the MMR, PaO2 and SaO2 were significantly higher and PaCO2 and HCO3- were significantly lower than baseline for 1 to 2 min of ventilation. This proof-of-concept study showed the LMA is an effective means of ventilating neonatal calves, as was the MMR

Upregulation of the cell-cycle regulator RGC-32 in Epstein-Barr virus-immortalized cells

Epstein-Barr virus (EBV) is implicated in the pathogenesis of multiple human tumours of lymphoid and epithelial origin. The virus infects and immortalizes B cells establishing a persistent latent infection characterized by varying patterns of EBV latent gene expression (latency 0, I, II and III). The CDK1 activator, Response Gene to Complement-32 (RGC-32, C13ORF15), is overexpressed in colon, breast and ovarian cancer tissues and we have detected selective high-level RGC-32 protein expression in EBV-immortalized latency III cells. Significantly, we show that overexpression of RGC-32 in B cells is sufficient to disrupt G2 cell-cycle arrest consistent with activation of CDK1, implicating RGC-32 in the EBV transformation process. Surprisingly, RGC-32 mRNA is expressed at high levels in latency I Burkitt's lymphoma (BL) cells and in some EBV-negative BL cell-lines, although RGC-32 protein expression is not detectable. We show that RGC-32 mRNA expression is elevated in latency I cells due to transcriptional activation by high levels of the differentially expressed RUNX1c transcription factor. We found that proteosomal degradation or blocked cytoplasmic export of the RGC-32 message were not responsible for the lack of RGC-32 protein expression in latency I cells. Significantly, analysis of the ribosomal association of the RGC-32 mRNA in latency I and latency III cells revealed that RGC-32 transcripts were associated with multiple ribosomes in both cell-types implicating post-initiation translational repression mechanisms in the block to RGC-32 protein production in latency I cells. In summary, our results are the first to demonstrate RGC-32 protein upregulation in cells transformed by a human tumour virus and to identify post-initiation translational mechanisms as an expression control point for this key cell-cycle regulator

Optimizing sequencing protocols for leaderboard metagenomics by combining long and short reads.

As metagenomic studies move to increasing numbers of samples, communities like the human gut may benefit more from the assembly of abundant microbes in many samples, rather than the exhaustive assembly of fewer samples. We term this approach leaderboard metagenome sequencing. To explore protocol optimization for leaderboard metagenomics in real samples, we introduce a benchmark of library prep and sequencing using internal references generated by synthetic long-read technology, allowing us to evaluate high-throughput library preparation methods against gold-standard reference genomes derived from the samples themselves. We introduce a low-cost protocol for high-throughput library preparation and sequencing

Echinoderms have bilateral tendencies

Echinoderms take many forms of symmetry. Pentameral symmetry is the major form and the other forms are derived from it. However, the ancestors of echinoderms, which originated from Cambrian period, were believed to be bilaterians. Echinoderm larvae are bilateral during their early development. During embryonic development of starfish and sea urchins, the position and the developmental sequence of each arm are fixed, implying an auxological anterior/posterior axis. Starfish also possess the Hox gene cluster, which controls symmetrical development. Overall, echinoderms are thought to have a bilateral developmental mechanism and process. In this article, we focused on adult starfish behaviors to corroborate its bilateral tendency. We weighed their central disk and each arm to measure the position of the center of gravity. We then studied their turning-over behavior, crawling behavior and fleeing behavior statistically to obtain the center of frequency of each behavior. By joining the center of gravity and each center of frequency, we obtained three behavioral symmetric planes. These behavioral bilateral tendencies might be related to the A/P axis during the embryonic development of the starfish. It is very likely that the adult starfish is, to some extent, bilaterian because it displays some bilateral propensity and has a definite behavioral symmetric plane. The remainder of bilateral symmetry may have benefited echinoderms during their evolution from the Cambrian period to the present

A two-domain elevator mechanism for sodium/proton antiport

Sodium/proton (Na+/H+) antiporters, located at the plasma membrane in every cell, are vital for cell homeostasis1. In humans, their dysfunction has been linked to diseases, such as hypertension, heart failure and epilepsy, and they are well-established drug targets2. The best understood model system for Na+/H+ antiport is NhaA from Escherichia coli1, 3, for which both electron microscopy and crystal structures are available4, 5, 6. NhaA is made up of two distinct domains: a core domain and a dimerization domain. In the NhaA crystal structure a cavity is located between the two domains, providing access to the ion-binding site from the inward-facing surface of the protein1, 4. Like many Na+/H+ antiporters, the activity of NhaA is regulated by pH, only becoming active above pH 6.5, at which point a conformational change is thought to occur7. The only reported NhaA crystal structure so far is of the low pH inactivated form4. Here we describe the active-state structure of a Na+/H+ antiporter, NapA from Thermus thermophilus, at 3 Å resolution, solved from crystals grown at pH 7.8. In the NapA structure, the core and dimerization domains are in different positions to those seen in NhaA, and a negatively charged cavity has now opened to the outside. The extracellular cavity allows access to a strictly conserved aspartate residue thought to coordinate ion binding1, 8, 9 directly, a role supported here by molecular dynamics simulations. To alternate access to this ion-binding site, however, requires a surprisingly large rotation of the core domain, some 20° against the dimerization interface. We conclude that despite their fast transport rates of up to 1,500 ions per second3, Na+/H+ antiporters operate by a two-domain rocking bundle model, revealing themes relevant to secondary-active transporters in general

A Differential Innate Immune Response in Active and Chronic Stages of Bovine Infectious Digital Dermatitis

Digital dermatitis (DD) commonly associated with Treponema spp. infection is a prevalent infectious bovine foot disease characterized by ulcerative and necrotic lesions. Lesions associated with DD are often classified using the M-stage scoring system, with M0 indicating healthy heel skin and M4 indicating chronic lesions. Current treatments utilizing antimicrobials or chemical footbaths are often ineffective and rarely cure DD lesions. Understanding the function of the innate immune response in the pathogenesis of DD will help to identify novel therapeutic approaches. In this study, the expression of the local innate host defense peptides cathelicidins and β-defensins was investigated in cows with DD and associated with the presence of treponemes and inflammatory reactions. Samples from active ulcerative DD lesions (M2) had considerable epidermal neutrophilic infiltration and increased gene expression of β-defensin tracheal antimicrobial peptides compared to control skin. Samples from acute lesions also had elevated local Cxcl-8 and TLR4 gene expression and abundant treponemes as identified by direct visualization, immunohistochemistry, and culture. Conversely, the anti-inflammatory peptide IL-10 was elevated in skin from chronic (M4) lesions, whereas bovine cathelicidin myeloid antimicrobial peptide 28 (Bmap-28) was increased in skin from oxytetracycline-treated M2 lesions. Experiments using cultured human keratinocytes challenged with Treponema spp. isolated from clinical cases of bovine DD showed that structural products from treponemes are able to initiate the innate immune response, in part through TLR2 signaling. These findings indicate that neutrophil influx, Cxcl-8, and β-defensin are key markers of active DD. Cathelicidins and IL-10 seem important in response to treatment or during the chronic proliferative stages of the disease

First report in italy of the exotic mosquito species Aedes (Finlaya) koreicus, a potential vector of arboviruses and filariae

BACKGROUND: In the Veneto region (north-eastern Italy) an entomological surveillance system has been implemented since the introduction of the Asian tiger mosquito (Aedes albopictus) in 1991. During the routine monitoring activity in a tiger mosquito-free area, an unexpected mosquito was noticed, which clearly did not belong to the recorded Italian fauna. FINDINGS: At the end of May 2011, twelve larvae and pupae were collected in a small village in Belluno province (Veneto region) from a single manhole. Ten adults reared in the laboratory were morphologically and genetically identified as Aedes (Finlaya) koreicus (Edwards, 1917), a species native to Southeast Asia. The subsequent investigations carried out in the following months in the same village provided evidence that this species had become established locally. Entomological and epidemiological investigations are currently ongoing in the surrounding area, to verify the eventual extension of the species outside the village and to trace back the route of entry into Italy. CONCLUSIONS: This is the first report in Italy of the introduction of the exotic mosquito Ae. koreicus. This species has been shown experimentally to be competent in the transmission of the Japanese encephalitis virus and of the dog heartworm Dirofilaria immitis and is considered a potential vector of other arboviruses. Thus, the establishment of this species may increase the current risk or pose new potential threats, for human and animal health. This finding considerably complicates the entomological monitoring of the Asian tiger mosquito Ae. albopictus in Italy and stresses the importance of implementing the entomological surveillance for the early detection of and the rapid response against invasive mosquito species

Discovery of Pulsed γ\gamma-rays from PSR J0034-0534 with the Fermi LAT: A Case for Co-located Radio and γ\gamma-ray Emission Regions

Millisecond pulsars (MSPs) have been firmly established as a class of gamma-ray emitters via the detection of pulsations above 0.1 GeV from eight MSPs by the Fermi Large Area Telescope (LAT). Using thirteen months of LAT data significant gamma-ray pulsations at the radio period have been detected from the MSP PSR J0034-0534, making it the ninth clear MSP detection by the LAT. The gamma-ray light curve shows two peaks separated by 0.274$\pm$0.015 in phase which are very nearly aligned with the radio peaks, a phenomenon seen only in the Crab pulsar until now. The $\geq$0.1 GeV spectrum of this pulsar is well fit by an exponentially cutoff power law with a cutoff energy of 1.8$\pm 0.6\pm$0.1 GeV and a photon index of 1.5$\pm 0.2\pm$0.1, first errors are statistical and second are systematic. The near-alignment of the radio and gamma-ray peaks strongly suggests that the radio and gamma-ray emission regions are co-located and both are the result of caustic formation.Comment: 20 pages, 3 figures, 2 tables. Accepted for publication in Ap

Ethnic differences in blood lipids and dietary intake between UK children of black African, black Caribbean, South Asian, and white European origin: the Child Heart and Health Study in England (CHASE).

BACKGROUND: Ischemic heart disease (IHD) rates are lower in UK black Africans and black Caribbeans and higher in South Asians when compared with white Europeans. Ethnic differences in lipid concentrations may play a part in these differences. OBJECTIVE: The objective was to investigate blood lipid and dietary patterns in UK children from different ethnic groups. DESIGN: This was a cross-sectional study in 2026 UK children (including 285 black Africans, 188 black Caribbeans, 534 South Asians, and 512 white Europeans) attending primary schools in London, Birmingham, and Leicester. We measured fasting blood lipid concentrations and collected 24-h dietary recalls. RESULTS: In comparison with white Europeans, black African children had lower total cholesterol (-0.14 mmol/L; 95% CI: -0.25, -0.04 mmol/L), LDL-cholesterol (-0.10 mmol/L; 95% CI: -0.20, -0.01 mmol/L), and triglyceride concentrations (proportional difference: -0.11 mmol/L; 95% CI: -0.16, -0.06 mmol/L); HDL-cholesterol concentrations were similar. Lower saturated fat intakes (-1.4%; 95% CI: -1.9%, -0.9%) explained the differences between total and LDL cholesterol. Black Caribbean children had total, LDL-cholesterol, HDL-cholesterol, and triglyceride concentrations similar to those for white Europeans, with slightly lower saturated fat intakes. South Asian children had total and LDL-cholesterol concentrations similar to those for white Europeans, lower HDL-cholesterol concentrations (-0.7 mmol/L; 95% CI: -0.11, -0.03 mmol/L), and elevated triglyceride concentrations (proportional difference: 0.14 mmol/L; 95% CI: 0.09, 0.20 mmol/L); higher polyunsaturated and monounsaturated fat intakes did not explain these lipid differences. CONCLUSIONS: Only black African children had a blood lipid profile and associated dietary pattern likely to protect against future IHD. The loss of historically lower LDL-cholesterol concentrations among UK black Caribbeans and South Asians may have important adverse consequences for future IHD risk in these groups