Infinity war : Trichomonas vaginalis and interactions with host immune response

Trichomonas vaginalis is the pathological agent of human trichomoniasis. The incidence is 156 million cases worldwide. Due to the increasing resistance of isolates to approved drugs and clinical complications that include increased risk in the acquisition and transmission of HIV, cervical and prostate cancer, and adverse out-comes during pregnancy, increasing our understanding of the patho-gen’s interaction with the host immune response is essential. Produc-tion of cytokines and cells of innate immunity: Neutrophils and mac-rophages are the main cells involved in the fight against the parasite, while IL-8, IL-6 and TNF-α are the most produced cytokines in re-sponse to this infection. Clinical complications: T. vaginalis increases the acquisition of HIV, stimulates the invasiveness and growth of prostate cells, and generates an inflammatory environment that may lead to preterm birth. Endosymbiosis: Mycoplasma hominis increased cytotoxicity, growth, and survival rate of the parasite. Purinergic sig-naling: NTPD-ases and ecto-5’-nucleotidase helps in parasite survival by modulating the nucleotides levels in the microenvironment. Anti-bodies: IgG was detected in serum samples of rodents infected with isolates from symptomatic patients as well as patients with symp-toms. However, antibody production does not protect against a rein-fection. Vaccine candidate targets: The transient receptor potential- like channel of T. vaginalis (TvTRPV), cysteine peptidase, and α-actinin are currently cited as candidate targets for vaccine develop-ment. In this context, the understanding of mechanisms involved in the host-T. vaginalis interaction that elicit the immune response may contribute to the development of new targets to combat trichomoni-asis

Novel treatment approaches to combat trichomoniasis, a neglected and sexually transmitted infection caused by trichomonas vaginalis : translational perspectives

The multistep translational science behind new drugs comprehends the entire process through laboratory, clinical, and community observations turned into health interventions. The development of new drug options from discovering targets and leading compounds in basic research for implementing therapeutic guidelines contributes to the emergence of health policies essential for infection control. This review updates the translational research in the scenario of the most common non-viral sexually transmitted infection (STI), trichomoniasis. Paradoxically to its high occurrence, it is considered neglected since notification is not mandatory. It turns into a stable disease with health complications, and receives little emphasis from public health programs to control STI. Although related to curable STIs, the current drugs, metronidazole and tinidazole, present therapeutic failures. The need for new options to treat trichomoniasis is established by basic research studies and patents revealing novel synthetic compounds and natural products presenting anti-Trichomonas vaginalis activities, mainly based on in vitro findings. Clinical trials are still focused on new routes of administration for conventional drugs. In addition, nanotechnology approaches are in their infancy, shedding light on potential possibilities for creating more effective, targeted, and safe delivery systems. Overall, the novel proposed approaches need, in addition to pharmaceutical development and efficacy assessments, to ensure that the quality requirements for their use as medicines are met. It is essential to overcome these issues to cross the “Death Valley” of drug discovery and to advance in the translational science criteria in the trichomoniasis drug development field

ALMA reveals the molecular gas properties of five star-forming galaxies across the main sequence at 3

International audienceWe present the detection of CO(5-4) with S/N> 7 - 13 and a lower CO transition with S/N > 3 (CO(4-3) for 4 galaxies, and CO(3-2) for one) with ALMA in band 3 and 4 in five main sequence star-forming galaxies with stellar masses 3-6x10^10 M/M_sun at 3 < z < 3.5. We find a good correlation between the total far-infrared luminosity LFIR and the luminosity of the CO(5-4) transition L'CO(5-4), where L'CO(5-4) increases with SFR, indicating that CO(5-4) is a good tracer of the obscured SFR in these galaxies. The two galaxies that lie closer to the star-forming main sequence have CO SLED slopes that are comparable to other star-forming populations, such as local SMGs and BzK star-forming galaxies; the three objects with higher specific star formation rates (sSFR) have far steeper CO SLEDs, which possibly indicates a more concentrated episode of star formation. By exploiting the CO SLED slopes to extrapolate the luminosity of the CO(1-0) transition, and using a classical conversion factor for main sequence galaxies of alpha_CO = 3.8 M_sun(K km s^-1 pc^-2)^-1, we find that these galaxies are very gas rich, with molecular gas fractions between 60 and 80%, and quite long depletion times, between 0.2 and 1 Gyr. Finally, we obtain dynamical masses that are comparable with the sum of stellar and gas mass (at least for four out of five galaxies), allowing us to put a first constraint on the alpha_CO parameter for main sequence galaxies at an unprecedented redshift

Whole exome sequencing highlights rare variants in CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1 as associated with FSHD

Introduction: Despite the progress made in the study of Facioscapulohumeral Dystrophy (FSHD), the wide heterogeneity of disease complicates its diagnosis and the genotype-phenotype correlation among patients and within families. In this context, the present work employed Whole Exome Sequencing (WES) to investigate known and unknown genetic contributors that may be involved in FSHD and may represent potential disease modifiers, even in presence of a D4Z4 Reduced Allele (DRA).Methods: A cohort of 126 patients with clinical signs of FSHD were included in the study, which were characterized by D4Z4 sizing, methylation analysis and WES. Specific protocols were employed for D4Z4 sizing and methylation analysis, whereas the Illumina® Next-Seq 550 system was utilized for WES. The study included both patients with a DRA compatible with FSHD diagnosis and patients with longer D4Z4 alleles. In case of patients harboring relevant variants from WES, the molecular analysis was extended to the family members.Results: The WES data analysis highlighted 20 relevant variants, among which 14 were located in known genetic modifiers (SMCHD1, DNMT3B and LRIF1) and 6 in candidate genes (CTCF, DNMT1, DNMT3A, EZH2 and SUV39H1). Most of them were found together with a permissive short (4–7 RU) or borderline/long DRA (8–20 RU), supporting the possibility that different genes can contribute to disease heterogeneity in presence of a FSHD permissive background. The segregation and methylation analysis among family members, together with clinical findings, provided a more comprehensive picture of patients.Discussion: Our results support FSHD pathomechanism being complex with a multigenic contribution by several known (SMCHD1, DNMT3B, LRIF1) and possibly other candidate genes (CTCF, DNMT1, DNMT3A, EZH2, SUV39H1) to disease penetrance and expressivity. Our results further emphasize the importance of extending the analysis of molecular findings within the proband’s family, with the purpose of providing a broader framework for understanding single cases and allowing finer genotype-phenotype correlations in FSHD-affected families

Performance of the First ANTARES Detector Line

In this paper we report on the data recorded with the first Antares detector line. The line was deployed on the 14th of February 2006 and was connected to the readout two weeks later. Environmental data for one and a half years of running are shown. Measurements of atmospheric muons from data taken from selected runs during the first six months of operation are presented. Performance figures in terms of time residuals and angular resolution are given. Finally the angular distribution of atmospheric muons is presented and from this the depth profile of the muon intensity is derived.Comment: 14 pages, 9 figure

Molecular, clinical, and muscle studies in myotonic dystrophy type 1 (DM1) associated with novel variant CCG expansions

We assessed clinical, molecular and muscle histopathological features in five unrelated Italian DM1 patients carrying novel variant pathological expansions containing CCG interruptions within the 3'-end of the CTG array at the DMPK locus, detected by bidirectional triplet primed PCR (TP-PCR) and sequencing. Three patients had a negative DM1 testing by routine long-range PCR; the other two patients were identified among 100 unrelated DM1 cases and re-evaluated to estimate the prevalence of variant expansions. The overall prevalence was 4.8&nbsp;% in our study cohort. There were no major clinical differences between variant and non-variant DM1 patients, except for cognitive involvement. Muscle RNA-FISH, immunofluorescence for MBNL1 and RT-PCR analysis documented the presence of ribonuclear inclusions, their co-localization with MBNL1, and an aberrant splicing pattern involved in DM1 pathogenesis, without any obvious differences between variant and non-variant DM1 patients. Therefore, this study shows that the CCG interruptions at the 3'-end of expanded DMPK alleles do not produce qualitative effects on the RNA-mediated toxic gain-of-function in DM1 muscle tissues. Finally, our results support the conclusion that different patterns of CCG interruptions within the CTG array could modulate the DM1 clinical phenotype, variably affecting the mutational dynamics of the variant repeat

Performance of the front-end electronics of the ANTARES neutrino telescope

ANTARES is a high-energy neutrino telescope installed in the Mediterranean Sea at a depth of 2475 m. It consists of a three-dimensional array of optical modules, each containing a large photomultiplier tube. A total of 2700 front-end ASICs named Analogue Ring Samplers (ARS) process the phototube signals, measure their arrival time, amplitude and shape as well as perform monitoring and calibration tasks. The ARS chip processes the analogue signals from the optical modules and converts information into digital data. All the information is transmitted to shore through further multiplexing electronics and an optical link. This paper describes the performance of the ARS chip; results from the functionality and characterization tests in the laboratory are summarized and the long-term performance in the apparatus is illustrated.Comment: 20 pages, 22 figures, published in Nuclear Instruments and Methods

«Testimoni di se stessi». Statuti dell'io nella poesia contemporanea

International audienceIntroduction aux études recuillies par le numéro 11 de la revue L'ospite ingrato, dans la section «Testimoni di se stessi». Statuti dell'io nella poesia contemporanea, portant sur la construction du sujet lyrique dans la poésie italienne contemporaine