Nanofluidic Platform for Studying the First-Order Phase Transitions in Superfluid Helium-3

The symmetry-breaking first-order phase transition between superfluid phases 3He-A and 3He-B can be triggered extrinsically by ionising radiation or heterogeneous nucleation arising from the details of the sample cell construction. However, the role of potential homogeneous intrinsic nucleation mechanisms remains elusive. Discovering and resolving the intrinsic processes may have cosmological consequences, since an analogous first-order phase transition, and the production of gravitational waves, has been predicted for the very early stages of the expanding Universe in many extensions of the Standard Model of particle physics. Here we introduce a new approach for probing the phase transition in superfluid 3He. The setup consists of a novel stepped-height nanofluidic sample container with close to atomically smooth walls. The 3He is confined in five tiny nanofabricated volumes and assayed non-invasively by NMR. Tuning of the state of 3He by confinement is used to isolate each of these five volumes so that the phase transitions in them can occur independently and free from any obvious sources of heterogeneous nucleation. The small volumes also ensure that the transitions triggered by ionising radiation are strongly suppressed. Here we present the preliminary measurements using this setup, showing both strong supercooling of 3He-A and superheating of 3He-B, with stochastic processes dominating the phase transitions between the two. The objective is to study the nucleation as a function of temperature and pressure over the full phase diagram, to both better test the proposed extrinsic mechanisms and seek potential parallel intrinsic mechanisms

SUMOylated SNF2PH promotes variant surface glycoprotein expression in bloodstream trypanosomes

SUMOylation is a post¿translational modification that positively regulates monoallelic expression of the trypanosome variant surface glycoprotein (VSG). The presence of a highly SUMOylated focus associated with the nuclear body, where the VSG gene is transcribed, further suggests an important role of SUMOylation in regulating VSG expression. Here, we show that SNF2PH, a SUMOylated plant homeodomain (PH)¿transcription factor, is upregulated in the bloodstream form of the parasite and enriched at the active VSG telomere. SUMOylation promotes the recruitment of SNF2PH to the VSG promoter, where it is required to maintain RNA polymerase I and thus to regulate VSG transcript levels. Further, ectopic overexpression of SNF2PH in insect forms, but not of a mutant lacking the PH domain, induces the expression of bloodstream stage¿specific surface proteins. These data suggest that SNF2PH SUMOylation positively regulates VSG monoallelic transcription, while the PH domain is required for the expression of bloodstream¿specific surface proteins. Thus, SNF2PH functions as a positive activator, linking expression of infective form surface proteins and VSG regulation, thereby acting as a major regulator of pathogenicity.The authors thank Dr. Alicia Barroso Del Jesus for excellent assistance and input with NSG methodology at the Genomic Unit and Dr. Laura Montosa at the Microscopy Unit (IPBLN-CSIC). This work was supported by grants from the Spanish Ministerio de Ciencia, Innovación y Universidades (RTI2018-098834-B-I00) and the Wellcome Trust (WTI 204697/Z/16/Z to MCF) and thegrant from the Argentinian National Agency for Promotion of Scientific and Technological Research to VEA (PICT/2016/0465)

NDM-5 and OXA-181 Beta-Lactamases, a Significant Threat Continues To Spread in the Americas

ABSTRACT Among Gram-negative bacteria, carbapenem-resistant infections pose a serious and life-threatening challenge. Here, the CRACKLE network reports a sentinel detection and characterization of a carbapenem-resistant Klebsiella pneumoniae ST147 isolate harboring bla NDM-5 and bla OXA-181 from a young man who underwent abdominal surgery in India. bla NDM-5 was located on an IncFII plasmid of ≈90 kb, whereas bla OXA-181 was chromosomally encoded. Resistome and genome analysis demonstrated multiple copies of the transposable element IS 26 and a “hot-spot region” in the IncFII plasmid

Family-centred music therapy with preterm infants and their parents in the Neonatal Intensive Care Unit (NICU) in Colombia – A mixed-methods study

This article reports a mixed-methods study of Music Therapy (MT) with preterm infants and their parents in a neonatal intensive care unit (NICU) in Colombia. The aim was to find out whether live MT during kangaroo care had an effect on the physiological outcomes of the neonates and would help parents to decrease their anxiety levels and improve parent–infant bonding. The participants were 36 medically stable neonates born between the 28th and 34th week of gestation and their parents. The quantitative data collection included heart rate, oxygen saturation, weight gain, length of hospitalization and re-hospitalization rate. The assessment measures for anxiety and bonding were the State-Trait Anxiety Inventory (STAI) and the Mother-to-Infant-Bonding Scale (MIBS). Thematic analysis was used to analyse the qualitative data collected with semi-structured interviews and questionnaires. The quantitative results showed statistically significant improvements in maternal state-anxiety (p = .007) and in the babies weight gain per day during the intervention period (p = .036). Positive trends were found regarding the babies’ length of hospitalization and re-hospitalization rate. Both parents improved their scores with the MIBS, but this was not statistically significant. The qualitative analysis showed that MT was important for parental well-being, for bonding and for fostering the development of the neonates. Interacting musically with their babies helped parents to experience feelings of connectedness and to distract themselves from their difficulties and from the noisy hospital environment

Identification and characterization of a novel non-structural protein of bluetongue virus

Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber

Quantitative principles of cis-translational control by general mRNA sequence features in eukaryotes.

BackgroundGeneral translational cis-elements are present in the mRNAs of all genes and affect the recruitment, assembly, and progress of preinitiation complexes and the ribosome under many physiological states. These elements include mRNA folding, upstream open reading frames, specific nucleotides flanking the initiating AUG codon, protein coding sequence length, and codon usage. The quantitative contributions of these sequence features and how and why they coordinate to control translation rates are not well understood.ResultsHere, we show that these sequence features specify 42-81% of the variance in translation rates in Saccharomyces cerevisiae, Schizosaccharomyces pombe, Arabidopsis thaliana, Mus musculus, and Homo sapiens. We establish that control by RNA secondary structure is chiefly mediated by highly folded 25-60 nucleotide segments within mRNA 5' regions, that changes in tri-nucleotide frequencies between highly and poorly translated 5' regions are correlated between all species, and that control by distinct biochemical processes is extensively correlated as is regulation by a single process acting in different parts of the same mRNA.ConclusionsOur work shows that general features control a much larger fraction of the variance in translation rates than previously realized. We provide a more detailed and accurate understanding of the aspects of RNA structure that directs translation in diverse eukaryotes. In addition, we note that the strongly correlated regulation between and within cis-control features will cause more even densities of translational complexes along each mRNA and therefore more efficient use of the translation machinery by the cell

Ciguatoxin occurrence in food-web components of a Cuban Coral Reef Ecosystem: Risk-assessment implications

In Cuba, ciguatera poisoning associated with fish consumption is the most commonly occurring non-bacterial seafood-borne illness. Risk management through fish market regulation has existed in Cuba for decades and consists of bans on selected species above a certain weight; however, the actual occurrence of ciguatoxins (CTXs) in seafood has never been verified. From this food safety risk management perspective, a study site locally known to be at risk for ciguatera was selected. Analysis of the epiphytic dinoflagellate community identified the microalga Gambierdiscus. Gambierdiscus species included six of the seven species known to be present in Cuba (G. caribaeus, G. belizeanus, G. carpenteri, G. carolinianus, G. silvae, and F. ruetzleri). CTX-like activity in invertebrates, herbivorous and carnivorous fishes were analyzed with a radioligand receptor-binding assay and, for selected samples, with the N2A cell cytotoxicity assay. CTX activity was found in 80% of the organisms sampled, with toxin values ranging from 2 to 8 ng CTX3C equivalents g−1 tissue. Data analysis further confirmed CTXs trophic magnification. This study constitutes the first finding of CTX-like activity in marine organisms in Cuba and in herbivorous fish in the Caribbean. Elucidating the structure–activity relationship and toxicology of CTX from the Caribbean is needed before conclusions may be drawn about risk exposure in Cuba and the wider Caribbean.info:eu-repo/semantics/publishedVersio

Stepped Care for Maternal Mental Health: A Case Study of the Perinatal Mental Health Project in South Africa

As one article in a series on Global Mental Health Practice, Simone Honikman and colleagues from South Africa provide a case study of the Perinatal Mental Health Project, which delivered mental health care to pregnant women in a collaborative, step-wise manner, making use of existing resources in primary care

The Atacama Cosmology Telescope: Two-Season ACTPol Spectra and Parameters

We present the temperature and polarization angular power spectra measured by the Atacama Cosmology Telescope Polarimeter (ACTPol). We analyze night-time data collected during 2013-14 using two detector arrays at 149 GHz, from 548 deg$^2$ of sky on the celestial equator. We use these spectra, and the spectra measured with the MBAC camera on ACT from 2008-10, in combination with Planck and WMAP data to estimate cosmological parameters from the temperature, polarization, and temperature-polarization cross-correlations. We find the new ACTPol data to be consistent with the LCDM model. The ACTPol temperature-polarization cross-spectrum now provides stronger constraints on multiple parameters than the ACTPol temperature spectrum, including the baryon density, the acoustic peak angular scale, and the derived Hubble constant. Adding the new data to planck temperature data tightens the limits on damping tail parameters, for example reducing the joint uncertainty on the number of neutrino species and the primordial helium fraction by 20%.Comment: 23 pages, 25 figure