Calciphylaxis in chronic, non-dialysis-dependent renal disease

BACKGROUND: Calciphylaxis cutis is characterized by media calcification of arteries and, most prominently, of cutaneous and subcutaneous arterioles occurring in renal insufficiency patients. CASE REPORT: A 53-year-old woman with chronic cardiac and renal failure complained of painful crural, non-varicosis ulcers. She was hospitalized in an immobilized condition due to both the crural ulcerations and the existing heart-failure state (NYHA III-IV) having pleural and pericardial effusions, atrial fibrillation and weight loss of 30 kg over the past year. Despite normalization of calcium-phosphorus balance and improvement of renal function, the clinical course of crural ulcerations deteriorated during the following 3 months. After failure of surgical debridements, multiple courses of sterile-maggot therapy were introduced at a late stage to stabilize the wounds. The patient died of recurrent wound infections and sepsis paralleled by exacerbations of renal malfunction. CONCLUSIONS: The role of renal disease in vascular complications is discussed. Sterile-maggot debridement may constitute a therapy for the ulcerated calciphylaxis at an earlier stage, i.e. when first ulcerations appear

Innovation in Creative Industries: From the Quadruple Helix Model to the Systems Theory

Knowledge and creativity have always played a key role in the economy. Since the 2000s, the relevance of the creative industries, a high growth sector, has been pointed out as long as its strong and positive effects on jobs and economic growth. In the current context of rapid globalization and technological development, the innovation system is getting even more complex because it implies a shift in research focus from the supply to the demand side environment (consumption-driven economy). The authors focus on theoretical approaches coming from management and media studies able to explain the current paradigm shift in innovation and knowledge production and use: the Triple Helix model (and its developments) and Systems Theory. As an interesting case study, the Creative Enterprise Australia (CEA) is analyzed according the theoretical approaches shown. The paper tries to shed new light on the evolving role of knowledge pointing out the overlapping relationships between all the actors involved and the interpenetration of systems, and the prominent appointment of the media as an interpretative framework of the convergence of the depicted theories

Bayesian probabilistic network modeling from multiple independent replicates

Often protein (or gene) time-course data are collected for multiple replicates. Each replicate generally has sparse data with the number of time points being less than the number of proteins. Usually each replicate is modeled separately. However, here all the information in each of the replicates is used to make a composite inference about signal networks. The composite inference comes from combining well structured Bayesian probabilistic modeling with a multi-faceted Markov Chain Monte Carlo algorithm. Based on simulations which investigate many different types of network interactions and experimental variabilities, the composite examination uncovers many important relationships within the networks. In particular, when the edge's partial correlation between two proteins is at least moderate, then the composite's posterior probability is large

Molecular Determinants of S100B Oligomer Formation

Background: S100B is a dimeric protein that can form tetramers, hexamers and higher order oligomers. These forms have been suggested to play a role in RAGE activation. Methodology/Principal Findings: Oligomerization was found to require a low molecular weight trigger/cofactor and could not be detected for highly pure dimer, irrespective of handling. Imidazol was identified as a substance that can serve this role. Oligomerization is dependent on both the imidazol concentration and pH, with optima around 90 mM imidazol and pH 7, respectively. No oligomerization was observed above pH 8, thus the protonated form of imidazol is the active species in promoting assembly of dimers to higher species. However, disulfide bonds are not involved and the process is independent of redox potential. The process was also found to be independent of whether Ca 2+ is bound to the protein or not. Tetramers that are purified from dimers and imidazol by gel filtration are kinetically stable, but dissociate into dimers upon heating. Dimers do not revert to tetramer and higher oligomer unless imidazol is again added. Both tetramers and hexamers bind the target peptide from p53 with retained stoichiometry of one peptide per S100B monomer, and with high affinity (lgK = 7.360.2 and 7.260.2, respectively in 10 mM BisTris, 5 mM CaCl 2, pH 7.0), which is less than one order of magnitude reduced compared to dimer under the same buffer conditions. Conclusion/Significance: S100B oligomerization requires protonated imidazol as a trigger/cofactor. Oligomers ar

Delimitation of Funga as a valid term for the diversity of fungal communities: the Fauna, Flora & Funga proposal (FF&F)

As public policies and conservation requirements for biodiversity evolve there is a need for a term for the kingdom Fungi equivalent to Fauna and Flora. Thisneed is considered to be urgent in order to simplify projects oriented toward implemention of educational and conservation goals. In an informal meeting held duringthe IX Congreso Latinoamericano de Micología by the authors, the idea of clarifying this matter initiated an extensive search of pertinent terminologies. As a result ofthese discussions and reviews, we propose that the word Funga be employed as an accurate and encompassing term for these purposes. This supports the proposal of thethree Fs, Fauna, Flora and Funga, to highlight parallel terminology referring to treatments of these macrorganism of particular geographical areas. Alternative terms andproposals are acknowledged and discussedFil: Kuhar, José Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto Multidisciplinario de Biología Vegetal. Universidad Nacional de Córdoba. Facultad de Ciencias Exactas Físicas y Naturales. Instituto Multidisciplinario de Biología Vegetal; ArgentinaFil: Furci, Giuliana. Fundación Fungi; ChileFil: Drechsler-Santos, Elisandro Ricardo. Universidade Federal de Santa Catarina; BrasilFil: Pfister, Donald H.. Harvard University; Estados Unido

Whodunnit? Electrophysiological correlates of agency judgements.

Sense of agency refers to the feeling that "I" am responsible for those external events that are directly produced by one's own voluntary actions. Recent theories distinguish between a non-conceptual "feeling" of agency linked to changes in the processing of self-generated sensory events, and a higher-order judgement of agency, which attributes sensory events to the self. In the current study we explore the neural correlates of the judgement of agency by means of electrophysiology. We measured event-related potentials to tones that were either perceived or not perceived as triggered by participants' voluntary actions and related these potentials to later judgements of agency over the tones. Replicating earlier findings on predictive sensory attenuation, we found that the N1 component was attenuated for congruent tones that corresponded to the learned action-effect mapping as opposed to incongruent tones that did not correspond to the previously acquired associations between actions and tones. The P3a component, but not the N1, directly reflected the judgement of agency: deflections in this component were greater for tones judged as self-generated than for tones judged as externally produced. The fact that the outcome of the later agency judgement was predictable based on the P3a component demonstrates that agency judgements incorporate early information processing components and are not purely reconstructive, post-hoc evaluations generated at time of judgement

Immunizations with diverse sarbecovirus receptor-binding domains elicit SARS-CoV-2 neutralizing antibodies against a conserved site of vulnerability.

Viral mutations are an emerging concern in reducing SARS-CoV-2 vaccination efficacy. Second-generation vaccines will need to elicit neutralizing antibodies against sites that are evolutionarily conserved across the sarbecovirus subgenus. Here, we immunized mice containing a human antibody repertoire with diverse sarbecovirus receptor-binding domains (RBDs) to identify antibodies targeting conserved sites of vulnerability. Antibodies with broad reactivity against diverse clade B RBDs targeting the conserved class 4 epitope, with recurring IGHV/IGKV pairs, were readily elicited but were non-neutralizing. However, rare class 4 antibodies binding this conserved RBD supersite showed potent neutralization of SARS-CoV-2 and all variants of concern. Structural analysis revealed that the neutralizing ability of cross-reactive antibodies was reserved only for those with an elongated CDRH3 that extends the antiparallel beta-sheet RBD core and orients the antibody light chain to obstruct ACE2-RBD interactions. These results identify a structurally defined pathway for vaccine strategies eliciting escape-resistant SARS-CoV-2 neutralizing antibodies

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT