NGF steers microglia toward a neuroprotective phenotype

Microglia are the sentinels of the brain but a clear understanding of the factors that modulate their activation in physiological and pathological conditions is still lacking. Here we demonstrate that Nerve Growth Factor (NGF) acts on microglia by steering them toward a neuroprotective and anti-inflammatory phenotype. We show that microglial cells express functional NGF receptors in vitro and ex vivo. Our transcriptomic analysis reveals how, in primary microglia, NGF treatment leads to a modulation of motility, phagocytosis and degradation pathways. At the functional level, NGF induces an increase in membrane dynamics and macropinocytosis and, in vivo, it activates an outward rectifying current that appears to modulate glutamatergic neurotransmission in nearby neurons. Since microglia are supposed to be a major player in Aβ peptide clearance in the brain, we tested the effects of NGF on its phagocytosis. NGF was shown to promote TrkA-mediated engulfment of Aβ by microglia, and to enhance its degradation. Additionally, the proinflammatory activation induced by Aβ treatment is counteracted by the concomitant administration of NGF. Moreover, by acting specifically on microglia, NGF protects neurons from the Aβ-induced loss of dendritic spines and inhibition of long term potentiation. Finally, in an ex-vivo setup of acute brain slices, we observed a similar increase in Aβ engulfment by microglial cells under the influence of NGF. Our work substantiates a role for NGF in the regulation of microglial homeostatic activities and points toward this neurotrophin as a neuroprotective agent in Aβ accumulation pathologies, via its anti-inflammatory activity on microglia

Mapping Cosmic Dawn and Reionization: Challenges and Synergies

Cosmic dawn and the Epoch of Reionization (EoR) are among the least explored observational eras in cosmology: a time at which the first galaxies and supermassive black holes formed and reionized the cold, neutral Universe of the post-recombination era. With current instruments, only a handful of the brightest galaxies and quasars from that time are detectable as individual objects, due to their extreme distances. Fortunately, a multitude of multi-wavelength intensity mapping measurements, ranging from the redshifted 21 cm background in the radio to the unresolved X-ray background, contain a plethora of synergistic information about this elusive era. The coming decade will likely see direct detections of inhomogenous reionization with CMB and 21 cm observations, and a slew of other probes covering overlapping areas and complementary physical processes will provide crucial additional information and cross-validation. To maximize scientific discovery and return on investment, coordinated survey planning and joint data analysis should be a high priority, closely coupled to computational models and theoretical predictions.Comment: 5 pages, 1 figure, submitted to the Astro2020 Decadal Survey Science White Paper cal

Calcitonin gene-related peptide decreases expression of HLA-DR and CD86 by human dendritic cells and dampens dendritic cell-driven T cell- proliferative responses via the type I calcitonin gene-related peptide receptor

These studies were performed to establish whether functional receptors for calcitonin gene-related peptide (CGRP) are present on human dendritic cells (DCs) and to investigate potential immunomodulatory effects of CGRP on DCs other than Langerhans cells. Reverse transcriptase-PCR revealed expression of mRNA for a type 1 CGRP receptor by mature and immature blood- derived DCs. Sequence analysis confirmed the identity of the type 1 CGRP receptor (CGRP-R1). Addition of CGRP (10-7 M) to mature and immature DCs resulted in mobilization of intracellular calcium. Treatment of immature DCs with CGRP (10-7 M), before and after maturation in monocyte-conditioned medium, resulted in decreased cell surface expression of HLA-DR MHC class II and the costimulatory molecule, CD86. Treatment of immature DCs with CGRP (10-7 M) also resulted in decreased expression of CD86, but expression of HLA-DR was unchanged. When CGRP-treated mature DCs were used to stimulate allogeneic T cells, proliferative responses were dampened (~50%), especially at low DC: T cell ratios (1:360). This effect was not observed with CGRP- treated, immature DCs. In contrast, CGRP-treated mature or immature DCs were no less efficient than untreated DCs in driving syngeneic T cell- proliferative responses to staphylococcal enterotoxin B. We conclude that mature and immature DCs express type 1 CGRP receptors and that signaling through these receptors may dampen mature DC-driven T cell proliferation most likely via down-regulation of CD86 and HLA-DR

Effects of different operating conditions on sediment slurry sequencing batch reactors treating marine port sediments contaminated by PAHs

Due to intensive anthropic activities, marine port sediments are often contaminated by organic pollutants like polycyclic aromatic hydrocarbons (PAHs), which represent a significant environmental threat. In this study, two sediment slurry sequencing batch reactors (SS-SBRs) were used to biologically degrade a mixture of PAHs (namely fluorene, phenanthrene, fluoranthene and pyrene) from marine sediments dredged from Cagliari (Italy) and El Kantaoui (Tunisia) ports. To enhance PAHs removal by biostimulation, nutrients were added in both sediments, acetate was used as co-substrate (El Kantaoui, SS-SBR1), and saponins were used as surfactants (Cagliari, SS-SBR2). Moreover, different levels of contamination (up to 200 mgPAHtot/kgdw in SS-SBR1; up to 400 mgPAHtot/kgdw in SS-SBR2) and solid to liquid ratios (S/L, up to 0.2 in SS-SBR1; up to 0.1 in SS-SBR2) were applied. As to SS-SBR1, the highest removal efficiencies (99-100% and 98-100% for 3- and 4-ring PAHs, respectively) were achieved when the level of contamination and S/L were set at 200 mgPAH-tot/kgdw and 0.1, 150 mgPAH-tot/kgdw and 0.13, and 150 mgPAH-tot/kgdw and 0.20, respectively; as to SS-SBR2, very high removal efficiencies (99÷100% and 98÷100% for 3- and 4-ring PAHs, respectively) were observed during the whole experimental campaign. Such results are promising and provide a useful background for testing other important operating parameters (e.g., the volumetric exchange ratio)

Adsorption and release of sulfamethizole from mesoporous silica nanoparticles functionalised with triethylenetetramine

Mesoporous silica nanoparticles (MSN) were synthesised and functionalised with tri-ethylenetetramine (MSN-TETA). The samples were fully characterised (transmission electron mi-croscopy, small angle X-ray scattering, Fourier transform infrared spectroscopy, thermogravimetric analysis, zeta potential and nitrogen adsorption/desorption isotherms) and used as carriers for the adsorption of the antimicrobial drug sulphamethizole (SMZ). SMZ loading, quantified by UV–Vis spectroscopy, was higher on MSN-TETA (345.8 mg g−1) compared with bare MSN (215.4 mg g−1) even in the presence of a lower surface area (671 vs. 942 m2 g−1). The kinetics of SMZ adsorption on MSN and MSN-TETA followed a pseudo-second-order model. The adsorption isotherm is described better by a Langmuir model rather than a Temkin or Freundlich model. Release kinetics showed a burst release of SMZ from bare MSN samples (k1 = 136 h−1) in contrast to a slower release found with MSN-TETA (k1 = 3.04 h−1), suggesting attractive intermolecular interactions slow down SMZ release from MSN-TETA. In summary, the MSN surface area did not influence SMZ adsorption and release. On the contrary, the design of an effective drug delivery system must consider the intermolecular interactions between the adsorbent and the adsorbate

Efficient Nitrogen Recovery from Agro-Energy Effluents for Cyanobacteria Cultivation (Spirulina)

The present study aimed to obtain an efficient liquid nitrogen fertilizer from the by-product of anaerobic digestion for its subsequent use in the production of cyanobacteria (Spirulina). A simple recovery technology was tested based on the stripping and acid absorption, modifying temperature (50 and 70 degrees C) and pH (10 and 12), of the ammonia nitrogen contained in the digestate produced in a large-scale plant treating livestock manure and grass silage. The results demonstrated how, at a relatively low temperature (50 degrees C), using sulfuric and citric acid solution, it is possible to recover nitrogen from a digestate in the form of ammonium sulfate and ammonium citrate with yields of 70% and 72.1% respectively. By carrying out Spirulina growth tests, promising results were obtained under semicontinuous production, with a maximum dry biomass daily productivity of 0.344 g L-1 day(-1) with ammonium sulfate and 0.246 gDW L-1 day(-1) with ammonium citrate. The results showed that nitrogen can be efficiently recovered on site by using the organic acid, digestate and waste heat from anaerobic digestion for Spirulina biomass production

Clinical characteristics, neuroimaging findings, and neuropsychological functioning in attention-deficit hyperactivity disorder: Sex differences

Recent clinical studies, in both children/adolescents and adults, have shown the extreme neuropsychological heterogeneity of attention-deficit hyperactivity disorder (ADHD): specific neuropsychological deficits have been found only in a minority of individuals, with no direct correlation between discrete cognitive performances and the trajectory of clinical symptoms. Deficits in specific neuropsychological functions may be common in ADHD, but nevertheless no cognitive or neuropsychological profile may fully explain the disorder. Sex differences in the ADHD presentation, both at a neuropsychological and clinical level, also contribute to this clinical and neuropsychological heterogeneity. At a neuropsychological level, females with ADHD may show greater working memory problems, poorer vocabulary skills and worse visual spatial reasoning. Structural and functional imaging study also show discrete differences across sex; however, the great majority of clinical studies mainly or exclusively include male participants with insufficient data to draw firm conclusions on sex differences within the disorder. Here, we report the recent literature data, discussing still open research questions about the clinical presentation, neuroimaging findings, and neuropsychological functioning in ADHD with a focus on the impact of sex differences—a deeper insight in these unresolved issues may have relevant clinical and therapeutic implications for tailored, effective, and long-lasting interventions

Contemporary diagnosis and treatment of conduct disorder in youth

Introduction: Conduct disorder (CD) is characterized by repetitive and persistent antisocial behaviors, being among the most frequently reported reasons of referral in youth. CD is a highly heterogeneous disorder, with possible specifiers defined according to age at onset, Limited Prosocial Emotions (LPE) otherwise known as Callous-Unemotional (CU) traits, Emotional Dysregulation (ED), and patterns of comorbidity, each with its own specific developmental trajectories. Areas covered: The authors review the evidence from published literature on the clinical presentations, diagnostic procedures, psychotherapeutic and psychoeducational approaches, and pharmacological interventions from RCT and naturalistic studies in youth. Evidence from studies including youths with LPE/CU traits, ED and aggression are also reviewed, as response moderators. Expert opinion: Due to its clinical heterogeneity, relevant subtypes of CD should be carefully characterized to gain reliable information on prognosis and treatments. Thus, disentangling this broad category in subtypes is crucial as a first step in diagnosis. Psychosocial interventions are the first option, possibly improving LPE/CU traits and ED, especially if implemented early during development. Instead, limited information, based on low-quality studies, supports pharmacological options. Second-generation antipsychotics, mood stabilizers, and stimulants are first-line medications, according to different target symptoms, such as aggression and emotional reactivity. Developmental pathways including ADHD suggest a specific role of psychostimulants

Bioleaching of Valuable Elements from Red Mud: A Study on the Potential of Non-Enriched Biomass

Red mud (RM) is the main residue produced by the alkaline extraction of alumina (Al2O3) from bauxite, and it contains valuable metals such as iron (Fe), aluminium (Al), titanium (Ti), magnesium (Mg), manganese (Mn), rare earth elements, etc. This research aimed to investigate the biologically induced leaching of some valuable elements from raw RM without preliminary biomass enrichment and inoculum, simultaneously reducing RM polluting potential and extracting metals for their subsequent recovery within a circular economy-based approach. In addition to the missing inoculum, such an approach is challenging since high RM alkalinity and pH, as well as the absence of any sulphides, constrain the use of the most common biohydrometallurgical techniques. Red Muds from two European locations were tested (RM-I and RM-II, respectively). Bioleaching tests were performed at different temperatures (T = 22 & DEG;C and 28 & DEG;C; and also 15 & DEG;C for RM-II) and solid-to-liquid ratios (S/L = 2%, 5%). A sudden drop in pH from alkaline to constant neutral/acidic values was observed in almost all tests, and such results were attributed to biological activity since abiotic tests did not show any pH decrease. The best results in terms of extraction were achieved with RM-II, in particular for Al, Mg and Mn (17%, 42% and 47%, respectively). At 2% S/L, the highest temperature allowed for a better metal release, while at 5% S/L, the highest extraction of Al, Mg and Ti was observed at 22 & DEG;C. As expected, iron was less available to leach at the achieved pH values, as it was mostly present as hematite in both RMs. Finally, the first microbiological characterisation of the autochthonous biomass selected during the bioleaching treatment of RM was provided