Radiation induced by relativistic electron showers in the X-ray spectrum of Active Galactic Nuclei

The iron Kα emitted from accreting black holes is thought to be produced by the reprocessing of hard X-ray radiation illuminating the disk. Mechanisms which could produce this hard X-ray radiation are magnetic reconnection in the disk corona or shocks. Both phenomena produce high energy particles whose contribution is usually ignored. In this work, we analyze how the transfer of mechanical energy from relativistic electrons to the circumnuclear gas (accretion disk, BLR) contributes to the X-ray continuum and the iron Kα emission. It is shown that for gas columns comparable to the Thomson depth, the iron Kα yield is comparable to that observed provided that the electron energy is above ∼600 keV and that the total kinetic luminosity of the beam is around log LKIN = 46.6−47.7; this luminosity is comparable to that observed in radio-loud AGNs. The photon index of the X-ray continuum (8 keV−20 keV) generated in such an electron shower is 1 ≤ Γ ≤ 2. Γ and the continuum strength are strongly model-dependent; they are dependent on both the relative orientation between the electron beam and the observer and the radius of the electron beam compared with the characteristic radius of the absorbing medium. The relevance of particle energy transport compared to photon energy transport in the AGN environment is outlined.Peer reviewe

Pretectal neurons control hunting behaviour

For many species, hunting is an innate behaviour that is crucial for survival, yet the circuits that control predatory action sequences are poorly understood. We used larval zebrafish to identify a population of pretectal neurons that control hunting. By combining calcium imaging with a virtual hunting assay, we identified a discrete pretectal region that is selectively active when animals initiate hunting. Targeted genetic labelling allowed us to examine the function and morphology of individual cells and identify two classes of pretectal neuron that project to ipsilateral optic tectum or the contralateral tegmentum. Optogenetic stimulation of single neurons of either class was able to induce sustained hunting sequences, in the absence of prey. Furthermore, laser ablation of these neurons impaired prey-catching and prevented induction of hunting by optogenetic stimulation of the anterior-ventral tectum. We propose that this specific population of pretectal neurons functions as a command system to induce predatory behaviour

The Leishmania infantum PUF proteins are targets of the humoral response during visceral leishmaniasis

<p>Abstract</p> <p>Background</p> <p>RNA-binding proteins of the PUF family share a conserved domain consisting of tandemly repeated 36-40 amino acid motifs (typically eight) known as Puf repeats. Proteins containing tandem repeats are often dominant targets of humoral responses during infectious diseases. Thus, we considered of interest to analyze whether <it>Leishmania </it>PUF proteins result antigenic during visceral leishmaniasis (VL).</p> <p>Findings</p> <p>Here, employing whole-genome databases, we report the composition, and structural features, of the PUF family in <it>Leishmania infantum</it>. Additionally, the 10 genes of the <it>L. infantum </it>PUF family were cloned and used to express the <it>Leishmania </it>PUFs in bacteria as recombinant proteins. Finally, the antigenicity of these PUF proteins was evaluated by determining levels of specific antibodies in sera from experimentally infected hamsters. The <it>Leishmania </it>PUFs were all recognized by the sera, even though with different degree of reactivity and/or frequency of recognition. The reactivity of hamster sera against recombinant LiPUF1 and LiPUF2 was particularly prominent, and these proteins were subsequently assayed against sera from human patients. High antibody responses against rLiPUF1 and rLiPUF2 were found in sera from VL patients, but these proteins resulted also recognized by sera from Chagas' disease patients.</p> <p>Conclusion</p> <p>Our results suggest that <it>Leishmania </it>PUFs are targets of the humoral response during <it>L. infantum </it>infection and may represent candidates for serodiagnosis and/or vaccine reagents; however, it should be kept in mind the cross-reactivity of LiPUFs with antibodies induced against other trypanosomatids such as <it>Trypanosoma cruzi</it>.</p

The SIDER2 elements, interspersed repeated sequences that populate the Leishmania genomes, constitute subfamilies showing chromosomal proximity relationship

<p>Abstract</p> <p>Background</p> <p>Protozoan parasites of the genus <it>Leishmania </it>are causative agents of a diverse spectrum of human diseases collectively known as leishmaniasis. These eukaryotic pathogens that diverged early from the main eukaryotic lineage possess a number of unusual genomic, molecular and biochemical features. The completion of the genome projects for three <it>Leishmania </it>species has generated invaluable information enabling a direct analysis of genome structure and organization.</p> <p>Results</p> <p>By using DNA macroarrays, made with <it>Leishmania infantum </it>genomic clones and hybridized with total DNA from the parasite, we identified a clone containing a repeated sequence. An analysis of the recently completed genome sequence of <it>L. infantum</it>, using this repeated sequence as bait, led to the identification of a new class of repeated elements that are interspersed along the different <it>L. infantum </it>chromosomes. These elements turned out to be homologues of SIDER2 sequences, which were recently identified in the <it>Leishmania major </it>genome; thus, we adopted this nomenclature for the <it>Leishmania </it>elements described herein. Since SIDER2 elements are very heterogeneous in sequence, their precise identification is rather laborious. We have characterized 54 LiSIDER2 elements in chromosome 32 and 27 ones in chromosome 20. The mean size for these elements is 550 bp and their sequence is G+C rich (mean value of 66.5%). On the basis of sequence similarity, these elements can be grouped in subfamilies that show a remarkable relationship of proximity, i.e. SIDER2s of a given subfamily locate close in a chromosomal region without intercalating elements. For comparative purposes, we have identified the SIDER2 elements existing in <it>L. major </it>and <it>Leishmania braziliensis </it>chromosomes 32. While SIDER2 elements are highly conserved both in number and location between <it>L. infantum </it>and <it>L. major</it>, no such conservation exists when comparing with SIDER2s in <it>L. braziliensis </it>chromosome 32.</p> <p>Conclusion</p> <p>SIDER2 elements constitute a relevant piece in the <it>Leishmania </it>genome organization. Sequence characteristics, genomic distribution and evolutionarily conservation of SIDER2s are suggestive of relevant functions for these elements in <it>Leishmania</it>. Apart from a proved involvement in post-trancriptional mechanisms of gene regulation, SIDER2 elements could be involved in DNA amplification processes and, perhaps, in chromosome segregation as centromeric sequences.</p

Efficiency gains due to network function sharing in CDN-as-a-Service slicing scenarios

Proceedings of: IEEE 7th International Conference on Network Softwarization (NetSoft), 28 June-2 July 2021, Tokyo, Japan.The consumption of video contents is currently dominating the traffic observed in ISP networks. The distribution of that content is usually performed leveraging on CDN caches storing and delivering multimedia. The advent of virtualization is bringing attention to the CDN as use case for virtualizing the cache function. In parallel, there is a trend on sharing network infrastructures as a way of reducing deployment costs by ISPs. Then, an interesting scenario emerges when considering the possibility of sharing virtualized cache functions among ISPs sharing a common physical infrastructure, mostly considering that usually those ISPs offer similar content catalogues to final end users. This paper investigates through simulations the potential efficiencies that can be achieved when sharing a virtual cache function if compared to the classical approach of independent virtual caches operated per ISP.This work has been partly funded by the project 5GROWTH (Grant Agreement no. 856709)

Leishmania infantum HSP70-II null mutant as candidate vaccine against leishmaniasis: a preliminary evaluation

<p>Abstract</p> <p>Background</p> <p>Visceral leishmaniasis is the most severe form of leishmaniasis and no effective vaccine exists. The use of live attenuated vaccines is emerging as a promising vaccination strategy.</p> <p>Results</p> <p>In this study, we tested the ability of a <it>Leishmania infantum </it>deletion mutant, lacking both <it>HSP70-II </it>alleles (ΔHSP70-II), to provide protection against <it>Leishmania </it>infection in the <it>L. major</it>-BALB/c infection model. Administration of the mutant line by either intraperitoneal, intravenous or subcutaneous route invariably leads to the production of high levels of NO and the development in mice of type 1 immune responses, as determined by analysis of anti-<it>Leishmania </it>IgG subclasses. In addition, we have shown that ΔHSP70-II would be a safe live vaccine as immunodeficient SCID mice, and hamsters (<it>Mesocricetus auratus</it>), infected with mutant parasites did not develop any sign of pathology.</p> <p>Conclusions</p> <p>The results suggest that the ΔHSP70-II mutant is a promising and safe vaccine, but further studies in more appropriate animal models (hamsters and dogs) are needed to appraise whether this attenuate mutant would be useful as vaccine against visceral leishmaniasis.</p

Effects of the disruption of the HSP70-II gene on the growth, morphology, and virulence of Leishmania infantum promastigotes

The 70-kDa heat shock protein (HSP70) is highly conserved among both prokaryotes and eukaryotes and plays essential roles in diverse cellular functions not only under stress but also under normal conditions. In the protozoan Leishmania infantum, the causative agent of visceral leishmaniasis, HSP70 is encoded by two HSP70 genes. Here, we describe the phenotypic alterations of HSP70-II-deficient (Deltahsp70-II) promastigotes. The absence of HSP70-II caused a major alteration in growth as the promastigotes reached stationary phase. In addition, aberrant forms were frequently observed in Deltahsp70-II mutant cultures. An accumulation of cells in the G2/M phase in cultures of the Deltahsp70-II mutant was determined by flow cytometry. Furthermore, Deltahsp70-II promastigotes showed a limited capacity of multiplication within macrophages, even though attachment to and uptake by macrophages did not differ significantly from the wild-type. Moreover, Deltahsp70-II was highly attenuated in BALB/c mouse experimental infections. In mutants re-expressing HSP70-II, the growth rate was restored, the normal morphology was recovered, and interactions with macrophages increased. However, promastigotes re-expressing HSP70-II did not recover their virulence. Overall, these data highlight the essential role played by HSP70-II expression in Leishmania virulence, pointing to this gene as a promising target for therapeutic interventions

The Leishmania HSP20 Is Antigenic during Natural Infections, but, as DNA Vaccine, It does not Protect BALB/c Mice against Experimental L. amazonensis Infection

Protozoa of the genus Leishmania are causative agents of leishmaniasis, an important health problem in both human and veterinary medicine. Here, we describe a new heat shock protein (HSP) in Leishmania, belonging to the small HSP (sHSP) family in kinetoplastids. The protein is highly conserved in different Leishmania species, showing instead significant divergence with sHSP's from other organisms. The humoral response elicited against this protein during Leishmania infection has been investigated in natural infected humans and dogs, and in experimentally infected hamsters. Leishmania HSP20 is a prominent antigen for canine hosts; on the contrary, the protein seems to be a poor antigen for human immune system. Time-course analysis of appearance of anti-HSP20 antibodies in golden hamsters indicated that these antibodies are produced at late stages of the infection, when clinical symptoms of disease are patent. Finally, the protective efficacy of HSP20 was assessed in mice using a DNA vaccine approach prior to challenge with Leishmania amazonensis