Absence of CD59 in guinea pigs: Analysis of the Cavia porcellus genome suggests the evolution of a CD59 pseudogene

CD59 is a membrane-bound regulatory protein that inhibits the assembly of the terminal membrane attack complex (C5b-9) of complement. From its original discovery in humans almost 30 years ago, CD59 has been characterized in a variety of species, from primates to early vertebrates, such as teleost fish. CD59 is ubiquitous in mammals; however, we have described circumstantial evidence suggesting that guinea pigs (Cavia porcellus) lack CD59, at least on erythrocytes. In this study, we have used a combination of phylogenetic analyses with syntenic alignment of mammalian CD59 genes to identify the only span of genomic DNA in C. porcellus that is homologous to a portion of mammalian CD59 and show that this segment of DNA is not transcribed. We describe a pseudogene sharing homology to exons 2 through 5 of human CD59 present in the C. porcellus genome. This pseudogene was flanked by C. porcellus homologs of two genes, FBXO3 and ORF91, a relationship and orientation that were consistent with other known mammalian CD59 genes. Analysis using RNA sequencing confirmed that this segment of chromosomal DNA was not transcribed. We conclude that guinea pigs lack an intact gene encoding CD59; to our knowledge, this is the first report of a mammalian species that does not express a functional CD59. The pseudogene we describe is likely the product of a genomic deletion event during its evolutionary divergence from other members of the rodent order

In Vitro Antioxidant and Antihypertensive Activity of Edible Insects Flours (Mealworm and Grasshopper) Fermented with Lactococcus lactis Strains

The objective of the present study was to evaluate the potential antioxidant and angiotensin converting enzyme inhibition (ACEI) activity of edible insect flours fermented with Lactococcus lactis strains. For the fermentation, mealworm and grasshoppers flours were dissolved (0.5% w/v) in buffer solution (pH 7.0) and individually inoculated (3%) with Lactococcus lactis strains (NRRL B-50571, NRRL B-50572). The samples were incubated for 72 h at 30 ◦C, and the pH was recorded. The degree of hydrolysis (DH) and protein content were determined. The total polyphenol compounds, antioxidant activity (ABTS, DPPH, ORAC, and FRAP), and ACEI of the \u3c3 kDa fractions were ana- lyzed. The pH of the fermented samples decreased to 3.5–3.9 (p \u3c 0.05). The fermented grasshopper flour showed an increased DH (0.42%) and overall higher total polyphenol content (8.23 mg Gallic Acid Equivalent/mL). In general, the highest antioxidant activity was for the grasshopper fractions fermented for 24 h by Lactococcus lactis NRRL B-50572, which also showed 23.47% ACEI inhibition with an IC50 of 0.97 mg/mL. The peptide profile obtained increased after fermentation, being higher for the mealworm flour fermented sample. This study presents, for the first time, the use of specific strains of Lactococus lactis for fermenting edible insect-derived products in the production of bioactive compounds with potential antioxidant and antihypertensive activity

Blocking Complement Factor B Activation Reduces Renal Injury and Inflammation in a Rat Brain Death Model

Introduction: The majority of kidneys used for transplantation are retrieved from brain-dead organ donors. In brain death, the irreversible loss of brain functions results in hemodynamic instability, hormonal changes and immunological activation. Recently, brain death has been shown to cause activation of the complement system, which is adversely associated with renal allograft outcome in recipients. Modulation of the complement system in the brain-dead donor might be a promising strategy to improve organ quality before transplantation. This study investigated the effect of an inhibitory antibody against complement factor B on brain death-induced renal inflammation and injury. Method: Brain death was induced in male Fischer rats by inflating a balloon catheter in the epidural space. Anti-factor B (anti-FB) or saline was administered intravenously 20 min before the induction of brain death (n = 8/group). Sham-operated rats served as controls (n = 4). After 4 h of brain death, renal function, renal injury, and inflammation were assessed. Results: Pretreatment with anti-FB resulted in significantly less systemic and local complement activation than in saline-treated rats after brain death. Moreover, anti-FB treatment preserved renal function, reflected by significantly reduced serum creatinine levels compared to saline-treated rats after 4 h of brain death. Furthermore, anti-FB significantly attenuated histological injury, as seen by reduced tubular injury scores, lower renal gene expression levels (>75%) and renal deposition of kidney injury marker-1. In addition, anti-FB treatment significantly prevented renal macrophage influx and reduced systemic IL-6 levels compared to saline-treated rats after brain death. Lastly, renal gene expression of IL-6, MCP-1, and VCAM-1 were significantly reduced in rats treated with anti-FB. Conclusion: This study shows that donor pretreatment with anti-FB preserved renal function, reduced renal damage and inflammation prior to transplantation. Therefore, inhibition of factor B in organ donors might be a promising strategy to reduce brain death-induced renal injury and inflammation.Nephrolog

Design of a high-performance optical tweezer for nanoparticle trapping

Integrated optical nanotweezers offer a novel paradigm for optical trapping, as their ability to confine light at the nanoscale leads to extremely high gradient forces. To date, nanotweezers have been realized either as photonic crystal or as plasmonic nanocavities. Here, we propose a nanotweezer device based on a hybrid photonic/plasmonic cavity with the goal of achieving a very high quality factor-to-mode volume (Q/V) ratio. The structure includes a 1D photonic crystal dielectric cavity vertically coupled to a bowtie nanoantenna. A very high Q/V ~ 107 (λ/n)−3 with a resonance transmission T = 29 % at λR = 1381.1 nm has been calculated by 3D finite element method, affording strong light–matter interaction and making the hybrid cavity suitable for optical trapping. A maximum optical force F = −4.4 pN, high values of stability S = 30 and optical stiffness k = 90 pN/nm W have been obtained with an input power Pin = 1 mW, for a polystyrene nanoparticle with a diameter of 40 nm. This performance confirms the high efficiency of the optical nanotweezer and its potential for trapping living matter at the nanoscale, such as viruses, proteins and small bacteria

Adaptive on-chip control of nano-optical fields with optoplasmonic vortex nanogates

A major challenge for plasmonics as an enabling technology for quantum information processing is the realization of active spatio-temporal control of light on the nanoscale. The use of phase-shaped pulses or beams enforces specific requirements for on-chip integration and imposes strict design limitations. We introduce here an alternative approach, which is based on exploiting the strong sub-wavelength spatial phase modulation in the near-field of resonantly-excited high-Q optical microcavities integrated into plasmonic nanocircuits. Our theoretical analysis reveals the formation of areas of circulating powerflow (optical vortices) in the near-fields of optical microcavities, whose positions and mutual coupling can be controlled by tuning the microcavities parameters and the excitation wavelength. We show that optical powerflow though nanoscale plasmonic structures can be dynamically molded by engineering interactions of microcavity-induced optical vortices with noble-metal nanoparticles. The proposed strategy of re-configuring plasmonic nanocircuits via locally-addressable photonic elements opens the way to develop chip-integrated optoplasmonic switching architectures, which is crucial for implementation of quantum information nanocircuits.Comment: 11 pages, 5 figure

Reductions in External Divalent Cations Evoke Novel Voltage-Gated Currents in Sensory Neurons

It has long been recognized that divalent cations modulate cell excitability. Sensory nerve excitability is of critical importance to peripheral diseases associated with pain, sensory dysfunction and evoked reflexes. Thus we have studied the role these cations play on dissociated sensory nerve activity. Withdrawal of both Mg2+ and Ca2+ from external solutions activates over 90% of dissociated mouse sensory neurons. Imaging studies demonstrate a Na+ influx that then causes depolarization-mediated activation of voltage-gated Ca2+ channels (CaV), which allows Ca2+ influx upon divalent re-introduction. Inhibition of CaV (ω-conotoxin, nifedipine) or NaV (tetrodotoxin, lidocaine) fails to reduce the Na+ influx. The Ca2+ influx is inhibited by CaV inhibitors but not by TRPM7 inhibition (spermine) or store-operated channel inhibition (SKF96365). Withdrawal of either Mg2+ or Ca2+ alone fails to evoke cation influxes in vagal sensory neurons. In electrophysiological studies of dissociated mouse vagal sensory neurons, withdrawal of both Mg2+ and Ca2+ from external solutions evokes a large slowly-inactivating voltage-gated current (IDF) that cannot be accounted for by an increased negative surface potential. Withdrawal of Ca2+ alone fails to evoke IDF. Evidence suggests IDF is a non-selective cation current. The IDF is not reduced by inhibition of NaV (lidocaine, riluzole), CaV (cilnidipine, nifedipine), KV (tetraethylammonium, 4-aminopyridine) or TRPM7 channels (spermine). In summary, sensory neurons express a novel voltage-gated cation channel that is inhibited by external Ca2+ (IC50∼0.5 µM) or Mg2+ (IC50∼3 µM). Activation of this putative channel evokes substantial cation fluxes in sensory neurons

CIBERER : Spanish national network for research on rare diseases: A highly productive collaborative initiative

Altres ajuts: Instituto de Salud Carlos III (ISCIII); Ministerio de Ciencia e Innovación.CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low-prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15-year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio

Global urban environmental change drives adaptation in white clover

Urbanization transforms environments in ways that alter biological evolution. We examined whether urban environmental change drives parallel evolution by sampling 110,019 white clover plants from 6169 populations in 160 cities globally. Plants were assayed for a Mendelian antiherbivore defense that also affects tolerance to abiotic stressors. Urban-rural gradients were associated with the evolution of clines in defense in 47% of cities throughout the world. Variation in the strength of clines was explained by environmental changes in drought stress and vegetation cover that varied among cities. Sequencing 2074 genomes from 26 cities revealed that the evolution of urban-rural clines was best explained by adaptive evolution, but the degree of parallel adaptation varied among cities. Our results demonstrate that urbanization leads to adaptation at a global scale