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The prevalent "core phonological deficit" model of dyslexia proposes that the reading and spelling difficulties characterizing affected children stem from prior developmental difficulties in processing speech sound structure, for example, perceiving and identifying syllable stress patterns, syllables, rhymes and phonemes. Yet spoken word production appears normal. This suggests an unexpected disconnect between speech input and speech output processes. Here we investigated the output side of this disconnect from a speech rhythm perspective by measuring the speech amplitude envelope (AE) of multisyllabic spoken phrases. The speech AE contains crucial information regarding stress patterns, speech rate, tonal contrasts and intonational information. We created a novel computerized speech copying task in which participants copied aloud familiar spoken targets like "Aladdin." Seventy-five children with and without dyslexia were tested, some of whom were also receiving an oral intervention designed to enhance multi-syllabic processing. Similarity of the child's productions to the target AE was computed using correlation and mutual information metrics. Similarity of pitch contour, another acoustic cue to speech rhythm, was used for control analyses. Children with dyslexia were significantly worse at producing the multi-syllabic targets as indexed by both similarity metrics for computing the AE. However, children with dyslexia were not different from control children in producing pitch contours. Accordingly, the spoken production of multisyllabic phrases by children with dyslexia is atypical regarding the AE. Children with dyslexia may not appear to listeners to exhibit speech production difficulties because their pitch contours are intact.

Canopy Homolog 2 (CNPY2) is an endoplasmic reticulum (ER) localized protein belonging to the CNPY gene family. We show here that CNPY2 is protective against ER stress induced by tunicamycin in neuronal cells. Overexpression of CNPY2 enhanced, while downregulation of CNPY2 using shRNA expression, reduced the viability of neuroblastoma cells after tunicamycin. Likewise, recombinant CNPY2 increased survival of cortical neurons in culture after ER stress. CNPY2 reduced the activating transcription factor 6 (ATF6) branch of ER stress and decreased the expression of CCAT/Enhancer-Binding Protein Homologous Protein (CHOP) involved in cell death. Immunostaining using mouse brain sections revealed that CNPY2 is expressed by cortical and striatal neurons and is co-expressed with the transcription factor, COUPTF-interacting protein 2 (CTIP2). In transgenic N171-82Q mice, as a model for Huntington’s disease (HD), the number of CNPY2-immunopositive neurons was increased in the cortex together with CTIP2. In the striatum, however, the number of CNPY2 decreased at 19 weeks of age, representing a late-stage of pathology. Striatal cells in culture were shown to be more susceptible to ER stress after downregulation of CNPY2. These results demonstrate that CNPY2 is expressed by corticostriatal neurons involved in the regulation of movement. CNPY2 enhances neuronal survival by reducing ER stress and is a promising factor to consider in HD and possibly in other brain diseases.

Background: A wealth of evidence underscores the bioactive properties of nutraceuticals and functional foods in addressing oxyinflammatory-based diseases with implications at both peripheral and central levels. Opuntia ficus-indica (OFI) is well-documented for its health-promoting attributes, though its fruit (OFIF) remains relatively understudied. Not only poses Metabolic Syndrome (MetS) cardiometabolic risks but also contributes significantly to cognitive impairment, especially in crucial brain areas such as hippocampus and hypothalamus. Methods: Following 8 weeks of HFD to induce MetS, rats received OFIF oral supplementation for 4 weeks to evaluate cognitive and affective modifications using behavioural paradigms, i.e. open field, burrowing, white-dark box, novelty-suppressed feeding, and object recognition tests. Our investigation extended to biochemical evaluations of lipid homeostasis, central and peripheral oxidative stress and neurotrophic pathways, correlating these measures together with circulating leptin levels. Results: Our data revealed that OFIF modulation of leptin positively correlates with systemic and brain oxidative stress, with markers of increased anxiety-like behaviour and impaired lipid homeostasis. On the other hand, leptin levels reduced by OFIF are associated with improved antioxidant barriers, declarative memory and neurotrophic signalling. Discussion: This study underscores OFIF neuroactive potential in the context of MetS-associated cognitive impairment, offering insights into its mechanisms and implications for future therapeutic strategies.

The cross-talk between plant-derived nanovesicles (PDNVs) and mammalian cells has been explored by several investigations, underlining the capability of these natural nanovesicles to regulate several molecular pathways. Additionally, PDNVs possess biological proprieties that make them applicable against pathological conditions, such as hepatic diseases. In this study we explored the antioxidant properties of lemon-derived nanovesicles, isolated at laboratory (LNVs) and industrial scale (iLNVs) in human healthy hepatocytes (THLE-2) and in metabolic syndrome induced by a high-fat diet (HFD) in the rat. Our findings demonstrate that in THLE-2 cells, LNVs and iLNVs decrease ROS production and upregulate the expression of antioxidant mediators, Nrf2 and HO-1. Furthermore, the in vivo assessment reveals that the oral administration of iLNVs improves glucose tolerance and lipid dysmetabolism, ameliorates biometric parameters and systemic redox homeostasis, and upregulates Nrf2/HO-1 signaling in HFD rat liver. Consequently, we believe LNVs/iLNVs might be a promising approach for managing hepatic and dysmetabolic disorders.

Slow cortical oscillations play a crucial role in processing the speech amplitude envelope, which is perceived atypically by children with developmental dyslexia. Here we use electroencephalography (EEG) recorded during natural speech listening to identify neural processing patterns involving slow oscillations that may characterize children with dyslexia. In a story listening paradigm, we find that atypical power dynamics and phase-amplitude coupling between delta and theta oscillations characterize dyslexic versus other child control groups (typically-developing controls, other language disorder controls). We further isolate EEG common spatial patterns (CSP) during speech listening across delta and theta oscillations that identify dyslexic children. A linear classifier using four delta-band CSP variables predicted dyslexia status (0.77 AUC). Crucially, these spatial patterns also identified children with dyslexia when applied to EEG measured during a rhythmic syllable processing task. This transfer effect (i.e., the ability to use neural features derived from a story listening task as input features to a classifier based on a rhythmic syllable task) is consistent with a core developmental deficit in neural processing of speech rhythm. The findings are suggestive of distinct atypical neurocognitive speech encoding mechanisms underlying dyslexia, which could be targeted by novel interventions.

Abstract Even prior to producing their first words, infants are developing a sophisticated speech processing system, with robust word recognition present by 4–6 months of age. These emergent linguistic skills, observed with behavioural investigations, are likely to rely on increasingly sophisticated neural underpinnings. The infant brain is known to robustly track the speech envelope, however previous cortical tracking studies were unable to demonstrate the presence of phonetic feature encoding. Here we utilise temporal response functions computed from electrophysiological responses to nursery rhymes to investigate the cortical encoding of phonetic features in a longitudinal cohort of infants when aged 4, 7 and 11 months, as well as adults. The analyses reveal an increasingly detailed and acoustically invariant phonetic encoding emerging over the first year of life, providing neurophysiological evidence that the pre-verbal human cortex learns phonetic categories. By contrast, we found no credible evidence for age-related increases in cortical tracking of the acoustic spectrogram.

From the perspective of circular economy, it is extremely useful to recycle waste products for human health applications. Among the health-beneficial properties of bioactive phyto-compounds, grape pomace represents a precious source of bioactive molecules with potential antitumor properties. Here, we describe the effects of a Sicilian grape pomace hydroalcoholic extract (HE) in colon and breast cancer cells. The characterization of HE composition revealed the predominance of anthoxanthins and phenolic acids. HE treatment was more effective in reducing the viability of colon cancer cells, while breast cancer cells appeared more resistant. Indeed, while colon cancer cells underwent apoptosis, as shown by DNA fragmentation, caspase-3 activation, and PARP1 degradation, breast cancer cells seemed to not undergo apoptosis. To elucidate the underlying mechanisms, reactive oxygen species (ROS) were evaluated. Interestingly, ROS increased in both cell lines but, while in colon cancer, cells’ ROS rapidly increased and progressively diminished over time, in breast cancer, cells’ ROS increase was persistent up to 24 h. This effect was correlated with the induction of pro-survival autophagy, demonstrated by autophagosomes formation, autophagic markers increase, and protection by the antioxidant NAC. The autophagy inhibitor bafilomycin A1 significantly increased the HE effects in breast cancer cells but not in colon cancer cells. Overall, our data provide evidence that HE efficacy in tumor cells depends on a balance between ROS-mediated autophagy and apoptosis. Therefore, inhibiting pro-survival autophagy may be a tool to target those cells that appear more resistant to the effect of HE.

We numerically analyze the feasibility of a platform-neutral, general strategy to perform quantum simulations of fermionic lattice field theories under open boundary conditions. The digital quantum simulator requires solely one- and two-qubit gates and is scalable since integrating each Hamiltonian term requires a finite (non-scaling) cost. The exact local fermion encoding we adopt relies on auxiliary $\mathbb{Z}_2$ lattice gauge fields by adding a pure gauge Hamiltonian term akin to the Toric Code. By numerically emulating the quantum simulator real-time dynamics, we observe a timescale separation for spin- and charge-excitations in a spin-$\frac{1}{2}$ Hubbard ladder in the $t-J$ model limit.

Abstract The activity of catalysts is mainly dictated by the adsorption strength of reaction intermediates at their surfaces. For electrocatalysts in solution, the adsorption strength is not only determined by the intrinsic properties of catalysts and reactants, but also by the solvation energy of reaction intermediates, which is difficult to capture with theoretical methods. Here, we report the impact of different explicit solvation approaches in estimating the stability of oxygenates on the (111) surface of platinum, widely used in oxygen electrocatalysis. We simulate the adsorption of OH, O, and OOH intermediates, relevant for oxygen reduction and oxygen evolution reactions, on Pt(111) with different solvation environments. We apply the static water bilayer model, typically adopted to calculate solvation energies on Pt(111) in computational studies. We then study the trend of solvation energies under different microsolvation environments, by adsorbing the intermediates in presence of an increasing number of water molecules. Last, we use a dynamic approach based on ab‐initio molecular dynamics (AIMD) to account for dynamic effects. Our results indicate that the stabilities of oxygenates approach those of the water bilayer when the number of molecules increases from zero to three, but the free energies are affected in a not trivial way by the morphology and size of the water cluster, due to the increased complexity and configurational space. Moreover, static methods imply overcorrected free energies. The adoption of a molecular dynamics approach, based on single‐run AIMD simulation of the Pt(111)/H2O interface, allows retrieval estimates close to the experimental observation, including dynamic effects, and is highly transferrable. These results suggest that i) when using a microsolvation scheme, it is recommended to include a few water molecules, up to three to resemble the picture of the static bilayer model; ii) dynamic effects are important and can be included with a single‐run AIMD scheme.

Abstract Exposures to fine particulate matter (PM $$_1$$ 1 ) have been associated with health impacts, but the understanding of the PM $$_1$$ 1 concentration-response (PM $$_1$$ 1 -CR) relationships, especially at low PM $$_1$$ 1 , remains incomplete. Here, we present novel data using a methodology to mimic lung exposure to ambient air (2 $$

We analyze cirrus cloud measurements from two dual-instrument cloud spectrometers, two hygrometers and a backscattersonde with the goal of connecting cirrus optical parameters usually accessible by remote sensing with microphysical size-resolved and bulk properties accessible in situ. Specifically, we compare the particle backscattering coefficient and depolarization ratio to the particle size distribution, effective and mean radius, surface area density, particle aspherical fraction, and ice water content. Data were acquired by instruments on board the M55 Geophysica research aircraft in July and August 2017 during the Asian Monsoon campaign based in Kathmandu, Nepal, in the framework of the StratoClim (Stratospheric and upper tropospheric processes for better climate predictions) project. Cirrus clouds have been observed over the Himalayan region between 10 km and the tropopause, situated at 17–18 km. The observed particle number densities varied between 10 and 10−4 cm−3 in the dimensional range from 1.5 to 468.5 µm in radius. Correspondingly, backscatter ratios from 1.1 up to 50 have been observed. Optical-scattering theory has been used to compare the backscattering coefficients computed from the measured particle size distribution with those directly observed by the backscattersonde. The aspect ratio of the particles, modeled as spheroids for the T-matrix approach, was left as a free parameter to match the calculations to the optical measures. The computed backscattering coefficient can be brought into good agreement with the observed one, but the match between simulated and measured depolarization ratios is insufficient. Relationships between ice particle concentration, mean and effective radius, surface area density, and ice water content with the measured backscattering coefficient are investigated for an estimate of the bulk microphysical parameters of cirrus clouds from remote sensing lidar data. The comparison between particle depolarization and aspherical fraction as measured by one of the cloud spectrometers equipped with a detector for polarization represents a novelty since it was the first time the two instruments were operated simultaneously on an aircraft. The analysis shows the difficulty of establishing an univocal link between depolarization values and the presence and amount of aspherical scatterers. This suggests the need for further investigation that could take into consideration not only the fraction of aspheric particles but also their predominant morphology.

Abstract The application of a mechanical strain to a 2D material can create pseudo-magnetic fields and lead to a quantized valley Hall effect. However, measuring valley-resolved effects remains a challenging task due to their inherent fragility and dependence on the sample’s proper design. Additionally, non-local transport probes based on multiterminal devices have often proven to be inadequate in yielding conclusive evidence of the valley Hall signal. Here, we introduce an alternative way of detecting the quantized valley Hall effect, which entirely relies on local density measurements, performed deep in the bulk of the sample. The resulting quantized signal is a genuine Fermi sea response, independent of the edge physics, and reflects the underlying valley Hall effect through the Widom-Středa formula. Specifically, our approach is based on measuring the variation of the particle density, locally in the bulk, upon varying the strength of the applied strain. This approach to the quantized valley Hall effect is particularly well suited for experiments based on synthetic lattices, where the particle density (or integrated density of states) can be spatially resolved.

Aerosol–cloud interactions play a crucial role in shaping Earth’s climate and hydrological cycle. Observing these interactions with high precision and accuracy is of the utmost importance for improving climate models and predicting Earth’s climate. Over the past few decades, lidar techniques have emerged as powerful tools for investigating aerosol–cloud interactions due to their ability to provide detailed vertical profiles of aerosol particles and clouds with high spatial and temporal resolutions. This review paper provides an overview of recent advancements in the study of ACI using lidar techniques. The paper begins with a description of the different cloud microphysical processes that are affected by the presence of aerosol, and with an outline of lidar remote sensing application in characterizing aerosol particles and clouds. The subsequent sections delve into the key findings and insights gained from lidar-based studies of aerosol–cloud interactions. This includes investigations into the role of aerosol particles in cloud formation, evolution, and microphysical properties. Finally, the review concludes with an outlook on future research. By reporting the latest findings and methodologies, this review aims to provide valuable insights for researchers engaged in climate science and atmospheric research.

Polar stratospheric clouds (PSCs) form in polar regions, typically between 15 and 25 km above mean sea level, when the local temperature is sufficiently low. PSCs play an important role in the ozone chemistry and the dehydration and denitrification of the stratosphere. Lidars with a depolarization channel may be used to detect and classify different classes of PSCs. The main PSC classes are water ice, nitric acid trihydrate (NAT), and supercooled ternary solutions (STSs), the latter being liquid droplets consisting of water, nitric acid, and sulfuric acid. PSCs have been observed at the lidar observatory at Concordia Station from 2014 onward. The harsh environmental conditions at Concordia during winter render successful lidar operation difficult. To facilitate the operation of the observatory, several measures have been put in place to achieve an almost complete remote control of the system. PSC occurrence is strongly correlated with local temperatures and is affected by dynamics, as the PSC coverage during the observation season shows. PSC observations in 2021 are shown as an example of the capability and functionality of the lidar observatory. A comparison of the observations with the satellite-borne CALIOP (Cloud-Aerosol Lidar with Orthogonal Polarization) lidar has been made to demonstrate the quality of the data and their representativeness for the Antarctic Plateau.

Polystyrene (PS) is an extremely stable polymer with a relatively high molecular weight and a strong hydrophobic character that makes it highly resistant to biodegradation. In this study, PS was subjected to biodegradation tests by Tenebrio Molitor (T. Molitor) and Zophobas Morio (Z. Morio) larvae. Specifically, six different experimental diets were compared: (i) T. Molitor fed with bran; (ii) T. Molitor fed only PS; (iii) T. Molitor fed only PS treated with H2O2; (iv) Z. Morio fed with bran; (v) Z. Morio fed only PS; and (vi) Z. Morio fed only PS treated with H2O2. Therefore, the mass change of the larvae and the survival rate were measured periodically, while the frass collected after 15 and 30 days was analyzed by different analyses, such as spectroscopy (FTIR), spectrometry (molecular weight and polydispersity), thermal analysis (TGA) and microscopy (scanning electron microscopy observations). The obtained results suggest that in the case of T. Molitor larvae, larvae feeding on bran showed the highest survival rate of ~94% at 30 days, while in the case of the Z. Morio larvae, the highest survival rate was exhibited by larvae eating PS-H2O2. Although not strongly pronounced, the Mw and Mn of PS in the frass of both T. Molitor and Z. Morio larvae decreased over 30 days, suggesting PS biodegradation. Finally, the morphological analysis shows that PS samples isolated from the frass of T. Molitor and Z. Morio larvae showed completely different, rough and irregularly carved surface structures, in comparison to PS before biodegradation.

Background: Ehlers-Danlos syndrome (EDS) is a hereditary collagen vascular disorder characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. Vascular EDS (vEDS) is a subtype of EDS which is characterized by vascular fragility.Case presentation: This is a case report of a young man with vEDS hospitalized for myocardial infarction. He was presented with a coronary dissection and developed aortic dissection, coronary rupture, and cardiac tamponade until death. Conclusion: This case report highlights how patients with vEDS and acute coronary syndrome show a higher risk of vascular complications compared with other patients, and their admission to the institution with a cardiac surgery room could be helpful and safe for better management of the complications. Non-invasive methods could be useful to exclude other vascular diseases, before the emergency coronary intervention.

We study if the Italian school system suffers from gender bias when judging students. To this aim, we use a differences-in-differences approach that compares the teachers' assessments and the standardized test scores that the students receive during the school year. We have census data for all Italian fifth and sixth graders in two different subjects, math and language, that include a rich set of additional controls. Our evidence reveals that, since primary school, boys are graded less favourably than girls in both math and language. This result is also confirmed for middle school students (sixth graders), and it holds even when (a) we separate the analysis between the most and least developed Italian regions, (b) we control for possible gender-specific attitude towards cheating and teachers' manipulation and (c) we introduce class and school fixed effects in the models. Comparing the results obtained across different levels of schooling and subjects, we cannot clearly identify the role of specific mechanisms in determining the gender bias. Overall the analysis suggests further study on the role of teachers' characteristics.

The transition to a more sustainable lifestyle requires a move away from petroleum-based sources and the investigation and funding of renewable and waste feedstocks to provide biobased sustainable materials. The formulation of films based on chitosan and microcrystalline cellulose with potential applications in the packaging sector has been demonstrated. Glycerol is also used as a plasticizer in the formulation of flexible films, while mucic acid is used as a valid alternative to acetic acid in such films. The film based on chitosan, microcrystalline cellulose, glycerol, and mucic acid shows properties and a performance similar to those of the film formulated with acetic acid, and, in addition, it seems that the photo-oxidation resistance of the film based on mucic acid is better than that of the material containing acetic acid. The films were characterized using spectroscopy (FTIR and UV-vis), tensile testing, water contact angle measurements, surface observations, and photo-oxidation resistance measurements. The presence of microcrystalline cellulose enhances the mechanical behavior, UV barrier properties, and surface hydrophobicity of the film. The feasibility of formulating chitosan-based films, with or without microcrystalline cellulose, which exhibit good properties and performances is demonstrated. Mucic acid instead of acetic acid is used in the formulation of these film.

In this study, we investigated the beneficial effects of grapefruit IntegroPectin, derived from industrial waste grapefruit peels via hydrodynamic cavitation, on microglia cells exposed to oxidative stress conditions. Grapefruit IntegroPectin fully counteracted cell death and the apoptotic process induced by cell exposure to tert-butyl hydroperoxide (TBH), a powerful hydroperoxide. The protective effects of the grapefruit IntegroPectin were accompanied with a decrease in the amount of ROS, and were strictly dependent on the activation of the phosphoinositide 3-kinase (PI3K)/Akt cascade. Finally, IntegroPectin treatment inhibited the neuroinflammatory response and the basal microglia activation by down-regulating the PI3K- nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB)- inducible nitric oxide synthase (iNOS) cascade. These data strongly support further investigations aimed at exploring IntegroPectin’s therapeutic role in in vivo models of neurodegenerative disorders, characterized by a combination of chronic neurodegeneration, oxidative stress and neuroinflammation.

Introduction: Long non-coding RNA H19 (lncH19) is highly expressed in colorectal cancer (CRC) and plays critical roles in tumor development, proliferation, metastasis, and drug resistance. Indeed, the expression of lncH19 usually affects the outcomes of chemo-, endocrine, and targeted therapies. ITF2357 (givinostat) is a histone deacetylase inhibitor (HDACi) that revealed a significant anti-tumor action by inducing apoptosis in different tumor models, including leukemia, melanoma, and glioblastoma. However, no data are present in the literature regarding the use of this compound for CRC treatment. Here, we investigate the role of lncH19 in ITF2357-induced apoptosis in CRC cells.Methods: The HCT-116 CRC cell line was stably silenced for H19 to investigate the role of this lncRNA in ITF2357-induced cell death. Cell viability assays and flow cytometric analyses were performed to assess the anti-proliferative and pro-apoptotic effects of ITF2357 in CRC cell lines that are silenced or not for lncH19. RT-PCR and Western blot were used to study the effects of ITF2357 on autophagy and apoptosis markers. Finally, bioinformatics analyses were used to identify miRNAs targeting pro-apoptotic factors that can be sponged by lncH19.Results: ITF2357 increased the expression levels of H19 and reduced HCT-116 cell viability, inducing apoptosis, as demonstrated by the increase in annexin-V positivity, caspase 3 cleavage, and poly (ADP-ribose) polymerase (PARP-1) degradation. Interestingly, the apoptotic effect of ITF2357 was much less evident in lncH19-silenced cells. We showed that lncH19 plays a functional role in the pro-apoptotic activity of the drug by stabilizing TP53 and its transcriptional targets, NOXA and PUMA. ITF2357 also induced autophagy in CRC cells, which was interpreted as a pro-survival response not correlated with lncH19 expression. Furthermore, ITF2357 induced apoptosis in 5-fluorouracil-resistant HCT-116 cells that express high levels of lncH19.Conclusion: This study shows that lncH19 expression contributes to ITF2357-induced apoptosis by stabilizing TP53. Overall, we suggest that lncH19 expression may be exploited to favor HDACi-induced cell death and overcome 5-fluorouracil chemoresistance.