Evaluation of AMCase and CHIT-1 expression in monocyte macrophages lineage

Acidic mammalian chitinase (AMCase) and chitotriosidase (CHIT-1) are two active chitinases expressed in humans. The chitinase activity of AMCase was found to be causative in allergic inflammation and its expression was found to be induced by interleukin-13. CHIT1-1 is expressed by phagocytic cells and extremely high levels are seen in lysosomal storage diseases. Despite that AMCase expression in the inflammation is under investigation, little is known regarding its regulation during macrophages' full maturation and polarization. In this study, we compared AMCase and CHIT-1 modulation during monocyte to macrophage transition and polarization. Gene expression analysis was investigated by real-time PCR from mRNA of human monocytes obtained from buffy coat of healthy volunteers, from mRNA of polarized to classically activated macrophages (or M1), obtained by interferon (IFN)-γ and lipopolysaccharide (LPS) treatment, and from mRNA of alternatively activated macrophages (or M2) obtained by interleukin (IL)-4 exposure. Our results showed that the expression of AMCase and CHIT-1 were differently modulated in HMMs at different stage of maturation. The behavior of these two active chitinase suggests that in the immune response their role is complementary.     

Nusinersen treatment and cerebrospinal fluid neurofilaments: An explorative study on Spinal Muscular Atrophy type 3 patients

The antisense oligonucleotide Nusinersen has been recently licensed to treat spinal muscular atrophy (SMA). Since SMA type 3 is characterized by variable phenotype and milder progression, biomarkers of early treatment response are urgently needed. We investigated the cerebrospinal fluid (CSF) concentration of neurofilaments in SMA type 3 patients treated with Nusinersen as a potential biomarker of treatment efficacy. The concentration of phosphorylated neurofilaments heavy chain (pNfH) and light chain (NfL) in the CSF of SMA type 3 patients was evaluated before and after six months since the first Nusinersen administration, performed with commercially available enzyme-linked immunosorbent assay (ELISA) kits. Clinical evaluation of SMA patients was performed with standardized motor function scales. Baseline neurofilament levels in patients were comparable to controls, but significantly decreased after six months of treatment, while motor functions were only marginally ameliorated. No significant correlation was observed between the change in motor functions and that of neurofilaments over time. The reduction of neurofilament levels suggests a possible early biochemical effect of treatment on axonal degeneration, which may precede changes in motor performance. Our study mandates further investigations to assess neurofilaments as a marker of treatment response.     

Evaluation of Cervical Cancer Screening Programs in C?te d’Ivoire,Guyana, and Tanzania: Effect of HIV Status

Background

HIV infection increases a woman’s risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study’s objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women.

Methods

A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d’Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant.

Findings

VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis—controlling for HIV status, location of the screening clinic, facility location, facility type, and country—compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P<0.0001) and of having large lesions requiring referral (OR 1.93, 95% CI 1.49, 2.51, P< 0.0001). Minor treatment complications occurred in 19 of 3,032 (0.63%) women; none required further intervention.

Conclusions

This study found that compared to HIV-uninfected/unknown women, HIV-infected women had nearly twice the odds of being VIA-positive and to require referral for large lesions. SVA was safe and resulted in significant reductions in loss to follow-up. There is increased need for excisional treatment in countries with high HIV prevalence.     

Escape of Sgs1 from Rad9 inhibition reduces the requirement for Sae2 and functional MRX in DNA end resection

Homologous recombination requires nucleolytic degradation (resection) of DNA double‐strand break (DSB) ends. In Saccharomyces cerevisiae, the MRX complex and Sae2 are involved in the onset of DSB resection, whereas extensive resection requires Exo1 and the concerted action of Dna2 and Sgs1. Here, we show that the checkpoint protein Rad9 limits the action of Sgs1/Dna2 in DSB resection by inhibiting Sgs1 binding/persistence at the DSB ends. When inhibition by Rad9 is abolished by the Sgs1‐ss mutant variant or by deletion of RAD9, the requirement for Sae2 and functional MRX in DSB resection is reduced. These results provide new insights into how early and long‐range resection is coordinated.     

Comparative study on the gametophyte morphology and development of three paramo species of Jamesonia (Pteridaceae,Polypodiopsida)

The sexual phase of three species of Jamesonia (J. imbricata, J. rotundifolia and J. scammaniae) has been studied, from spore germination to gametangia formation, with special attention to the morphological development of prothalli. This is the first work to deal with gametophytes of species in this genus. All three species have trilete, tetrahedrical spores that germinate following the Vittaria type. The developmental pattern of J. imbricata and J. rotundifolia is intermediate between the Adiantum and Ceratopteris types, as the initial mitotic activity is assumed by an obconical apical cell, substituted later by a lateral meristem. In J. scammaniae, no apical cell or lateral meristem is formed, so the prothalli remain ameristic throughout the developmental process. Adult gametophytes are naked and variable in shape, in the same species ranging from typical cordate prothalli to irregularly lobed forms. Gametangia of normal shape and size was observed in both J. imbricata and J. rotundifolia, but not in J. scammaniae. Apogamy could be expected to occur in the genus, a phenomenon to be examined in the future. Comparisons are made with known species of related genera and results are discussed from an ecological perspective in the paramo environment.     

Effects of bottom trawling on fish foraging and feeding

The effects of bottom trawling on benthic invertebrates include reductions of biomass, diversity and body size. These changes may negatively affect prey availability for demersal fishes, potentially leading to reduced food intake, body condition and yield of fishes in chronically trawled areas. Here, the effect of trawling on the prey availability and diet of two commercially important flatfish species, plaice (Pleuronectes platessa) and dab (Limanda limanda), was investigated over a trawling intensity gradient in the Irish Sea. Previous work in this area has shown that trawling negatively affects the condition of plaice but not of dab. This study showed that reductions in local prey availability did not result in reduced feeding of fish. As trawling frequency increased, both fish and prey biomass declined, such that the ratio of fish to prey remained unchanged. Consequently, even at frequently trawled sites with low prey biomass, both plaice and dab maintained constant levels of stomach fullness and gut energy contents. However, dietary shifts in plaice towards energy-poor prey items were evident when prey species were analysed individually. This, together with a potential decrease in foraging efficiency due to low prey densities, was seen as the most plausible cause for the reduced body condition observed. Understanding the relationship between trawling, benthic impacts, fish foraging and resultant body condition is an important step in designing successful mitigation measures for future management strategies in bottom trawl fisheries.     

Effect of 17β-estradiol on calcium response to phytohaemagglutinin in human lymphocytes

Pre-treatment of human lymphocytes with 17-estradiol diminishes the increase in concentration of cytosolic free calcium after stimulation with phytohaemagglutinin. The effect is dependent on 17-estradiol concentration and on the preincubation time. The effect is not due to an interaction between 17-estradiol and phytohaemagglutinin, but appears to be a consequence of the binding of the hormone to the cell surface. The effect is specific for 17-estradiol, since the isomer and other steroid hormones (progesterone, testosterone, diethylstilbestrol and 5-androstan), have no effect. Since the effect of the 17-estradiol can be suppressed by treatment of lymphocytes with ouabain, it appears that the effect of estradiol on the rise of cytosolic calcium induced by phytohaemagglutinin is mediated by the (Na, K)-ATPase.