Gadolinium deposition disease: Initial description of a disease that has been around for a while

AbstractPurposeTo describe the clinical manifestations of presumed gadolinium toxicity in patients with normal renal function.Materials and methodsParticipants were recruited from two online gadolinium toxicity support groups. The survey was anonymous and individuals were instructed to respond to the survey only if they had evidence of normal renal function, evidence of gadolinium in their system beyond 30days of this MRI, and no pre-existent clinical symptoms and/or signs of this type.Results42 subjects responded to the survey (age: 28–69, mean 49.1±22.4years). The most common findings were: central pain (n=15), peripheral pain (n=26), headache (n=28), and bone pain (n=26). Only subjects with distal leg and arm distribution described skin thickening (n=22). Clouded mentation and headache were the symptoms described as persistent beyond 3months in 29 subjects. Residual disease was present in all patients. Twenty-eight patients described symptoms following administration of one brand of Gadolinium-Based Contrast Agent (GBCA), 21 after a single GBCA administration and 7 after multiple GBCA administrations, including: gadopentetate dimeglumine, n=9; gadodiamide, n=4; gadoversetamide, n=4; gadobenate dimeglumine, n=4; gadobutrol, n=1; gadoteridol, n=2; and unknown, n=4.ConclusionsGadolinium toxicity appears to arise following GBCA administration, which appears to contain clinical features seen in Nephrogenic Systemic Fibrosis, but also features not observed in that condition

Fractional Hardy-Sobolev type inequalities for half spaces and John domains

As our main result we prove a variant of the fractional Hardy-Sobolev-Maz'ya inequality for half spaces. This result contains a complete answer to a recent open question by Musina and Nazarov. In the proof we apply a new version of the fractional Hardy-Sobolev inequality that we establish also for more general unbounded John domains than half spaces

Kinship and intragroup social dynamics in two sympatric African Colobus species

SFRH/BPD/87396/2012 UID/ANT/04038/2013Kinship has been described as a major factor shaping primates’ social dynamics, with individuals biasing their affiliative interactions to their related counterparts. However, it has also been demonstrated that, under certain circumstances, social bonding can be established in the absence of kin. The fact that Colobus polykomos (western black-and-white colobus) and Procolobus badius temminckii (Temminck’s red colobus) often live in sympatry (subject to the same ecological/anthropogenic pressures) but exhibit contrasting social systems makes them good models to test which factors shape their social systems. We investigated the influence of kinship on intragroup social dynamics of one focal group of each species present in Cantanhez National Park, Guinea-Bissau. Between October 2008 and June 2009 we used focal sampling to collect information on the individuals’ nearest neighbors and ad libitum sampling to collect data on intragroup social interactions. We estimated pairwise relatedness using fecal DNA from 9 individuals of Colobus polykomos and 15 individuals of Procolobus badius temminckii genotyped at 15 microsatellite loci. We found that, in the focal group of Colobus polykomos, individuals showed no preference to interact or be spatially closer to related partners. Moreover, mainly unrelated females and related males composed the focal group of Procolobus badius temminckii but grooming was most frequent among female dyads and only rarely involved male dyads. We conclude that kinship is not an important factor determining the social bonding in either study species, suggesting that other factors, e.g., anthropogenic, ecological, may be at play shaping these groups’ social bonding.authorsversionpublishe

Disarming Pseudomonas aeruginosa Virulence by the Inhibitory Action of 1,10-Phenanthroline-5,6-Dione- Based Compounds: Elastase B (LasB) as a Chemotherapeutic Target

negative pathogen Pseudomonas aeruginosa, and this enzyme orchestrates several physiopathological events during bacteria-host interplays. LasB is considered to be a potential target for the development of an innovative chemotherapeutic approach, especially against multidrug-resistant strains. Recently, our group showed that 1,10-phenanthroline-5,6-dione (phendione), [Ag(phendione)2]ClO4 (Ag-phendione) and [Cu(phendione)3](ClO4)2.4H2O (Cu-phendione) had anti-P. aeruginosa action against both planktonic- and biofilm-growing cells. In the present work, we have evaluated the effects of these compounds on the (i) interaction with the lasB active site using in silico approaches, (ii) lasB proteolytic activity by using a specific fluorogenic peptide substrate, (iii) lasB gene expression by real time-polymerase chain reaction, (iv) lasB protein secretion by immunoblotting, (v) ability to block the damages induced by lasB on a monolayer of lung epithelial cells, and (vi) survivability of Galleria mellonella larvae after being challenged with purified lasB and lasB-rich bacterial secretions. Molecular docking analyses revealed that phendione and its Ag+ and Cu2+ complexes were able to interact with the amino acids forming the active site of lasB, particularly Cu-phendione which exhibited the most favorable interaction energy parameters. Additionally, the test compounds were effective inhibitors of lasB activity, blocking the in vitro cleavage of the peptide substrate, aminobenzyl-Ala-Gly-Leu-Ala-p-nitrobenzylamide, with Cu- phendione having the best inhibitory action (Ki = 90 nM). Treating living bacteria with a sub-inhibitory concentration (1/2 × MIC value) of the test compounds caused a significant reduction in the expression of the lasB gene as well as its mature protein production/secretion. Further, Ag-phendione and Cu-phendione offered protective rg 1 August 2019 | Volume 10 | Article 1701 1,10-Phenanthroline-5,6-Dione-Based Compounds: As Anti-Virulence Drugs action for lung epithelial cells, reducing the A549 monolayer damage by approximately 32 and 42%, respectively. Interestingly, Cu-phendione mitigated the toxic effect of both purified lasB molecules and lasB-containing bacterial secretions in the in vivo model, increasing the survival time of G. mellonella larvae. Collectively, these data reinforce the concept of lasB being a veritable therapeutic target and phendione-based compounds (mainly Cu-phendione) being prospective anti-virulence drugs against P. aeruginosa

Profiling of human acquired immunity against the salivary proteins of Phlebotomus papatasi reveals clusters of differential immunoreactivity

Citation: Geraci, Nicholas S., Rami M. Mukbel, Michael T. Kemp, Mariha N. Wadsworth, Emil Lesho, Gwen M. Stayback, Matthew M. Champion, et al. 2014. “Profiling of Human Acquired Immunity Against the Salivary Proteins of Phlebotomus Papatasi Reveals Clusters of Differential Immunoreactivity.” The American Journal of Tropical Medicine and Hygiene 90 (5): 923–38. https://doi.org/10.4269/ajtmh.13-0130.Phlebotomus papatasi sand flies are among the primary vectors of Leishmania major parasites from Morocco to the Indian subcontinent and from southern Europe to central and eastern Africa. Antibody-based immunity to sand fly salivary gland proteins in human populations remains a complex contextual problem that is not yet fully understood. We profiled the immunoreactivities of plasma antibodies to sand fly salivary gland sonicates (SGSs) from 229 human blood donors residing in different regions of sand fly endemicity throughout Jordan and Egypt as well as 69 US military personnel, who were differentially exposed to P. papatasi bites and L. major infections in Iraq. Compared with plasma from control region donors, antibodies were significantly immunoreactive to five salivary proteins (12, 26, 30, 38, and 44 kDa) among Jordanian and Egyptian donors, with immunoglobulin G4 being the dominant anti-SGS isotype. US personnel were significantly immunoreactive to only two salivary proteins (38 and 14 kDa). Using k-means clustering, donors were segregated into four clusters distinguished by unique immunoreactivity profiles to varying combinations of the significantly immunogenic salivary proteins. SGS-induced cellular proliferation was diminished among donors residing in sand fly-endemic regions. These data provide a clearer picture of human immune responses to sand fly vector salivary constituents

Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab

This white paper summarizes the scientific opportunities for utilization of the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and associated experimental equipment at Jefferson Lab. It is based on the 52 proposals recommended for approval by the Jefferson Lab Program Advisory Committee.The upgraded facility will enable a new experimental program with substantial discovery potential to address important topics in nuclear, hadronic, and electroweak physics.Comment: 64 page

Emergence and evolution of Santa Maria Island (Azores)—The conundrum of uplifted islands revisited

The growth and decay of ocean island volcanoes is intrinsically linked to vertical movements; whilst the causes for subsidence are better understood, uplift mechanisms remain enigmatic. Santa Maria Island in the Azores Archipelago is an ocean island volcano resting on top of young lithosphere, barely 480 km away from the Mid-Atlantic Ridge. Like most other Azorean islands, Santa Maria should be experiencing subsidence. Yet, several features indicate an uplift trend instead. In this paper we reconstruct the evolutionary history of Santa Maria with respect to the timing and magnitude of its vertical movements, using detailed fieldwork and 40Ar/39Ar geochronology. Our investigations revealed a complex evolutionary history spanning ~6 m.y., with subsidence up to ca. 3.5 Ma followed by uplift extending to the present day. The fact that an island located in young lithosphere experienced a pronounced uplift trend is remarkable and raises important questions concerning possible uplift mechanisms. Localized uplift in response to the tectonic regime affecting the southeastern tip of the Azores Plateau is unlikely since the area is under transtension. Our analysis shows that the only viable mechanism able to explain the uplift is crustal thickening by basal intrusions, suggesting that intrusive processes play a significant role even on islands standing on young lithosphere, such as in the Azores