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Abstract Background Reduction of adult hippocampal neurogenesis is an early critical event in Alzheimer’s disease (AD), contributing to progressive memory loss and cognitive decline. Reduced levels of the nucleoporin 153 (Nup153), a key epigenetic regulator of NSC stemness, characterize the neural stem cells isolated from a mouse model of AD (3×Tg) (AD-NSCs) and determine their altered plasticity and gene expression. Methods Nup153-regulated mechanisms contributing to NSC function were investigated: (1) in cultured NSCs isolated from AD and wild type (WT) mice by proteomics; (2) in vivo by lentiviral-mediated delivery of Nup153 or GFP in the hippocampus of AD and control mice analyzing neurogenesis and cognitive function; (3) in human iPSC-derived brain organoids obtained from AD patients and control subjects as a model of neurodevelopment. Results Proteomic approach identified Nup153 interactors in WT- and AD-NSCs potentially implicated in neurogenesis regulation. Gene ontology (GO) analysis showed that Nup153-bound proteins in WT-NSCs were involved in RNA metabolism, nuclear import and epigenetic mechanisms. Nup153-bound proteins in AD-NSCs were involved in pathways of neurodegeneration, mitochondrial dysfunction, proteasomal processing and RNA degradation. Furthermore, recovery of Nup153 levels in AD-NSCs reduced the levels of oxidative stress markers and recovered proteasomal activity. Lentiviral-mediated delivery of Nup153 in the hippocampal niche of AD mice increased the proliferation of early progenitors, marked by BrdU/DCX and BrdU/PSANCAM positivity and, later, the integration of differentiating neurons in the cell granule layer (BrdU/NeuN+ cells) compared with GFP-injected AD mice. Consistently, Nup153-injected AD mice showed an improvement of cognitive performance in comparison to AD-GFP mice at 1 month after virus delivery assessed by Morris Water Maze. To validate the role of Nup153 in neurogenesis we took advantage of brain organoids derived from AD-iPSCs characterized by fewer neuroepithelial progenitor loops and reduced differentiation areas. The upregulation of Nup153 in AD organoids recovered the formation of neural-like tubes and differentiation. Conclusions Our data suggest that the positive effect of Nup153 on neurogenesis is based on a complex regulatory network orchestrated by Nup153 and that this protein is a valuable disease target.

Abstract The Russian invasion of Ukraine in 2022 triggered a global wheat price spike and food insecurities in import-dependent countries. We combine an analysis of the global wheat supply network with an agricultural commodity price model to investigate national impaired supplies and the global annual wheat price hike, respectively, for the trade year 2022. Using a scenario analysis, we show that international cooperation manifested in the Black Sea Grain and Solidarity Lanes initiatives and the removal of export restrictions may have mitigated the 2022 price hike by 13 percentage points. In a worst case scenario – characterized by multi-breadbasket harvest failures, escalating export restrictions, and blocked Ukrainian exports – wheat price increases by 90% compared to the 2000–2020 average. Coping strategies – such as food-secure countries dispersing stocks, reducing wheat as feed, or boosting wheat production – are effective at mitigating the price spike in simplified scenarios. Our findings underscore the imperative of coordinated policy responses to avoid global food supply disruptions.

Abstract Herbivorous insects alter biogeochemical cycling within forests, but the magnitude of these impacts, their global variation, and drivers of this variation remain poorly understood. To address this knowledge gap and help improve biogeochemical models, we established a global network of 74 plots within 40 mature, undisturbed broadleaved forests. We analyzed freshly senesced and green leaves for carbon, nitrogen, phosphorus and silica concentrations, foliar production and herbivory, and stand-level nutrient fluxes. We show more nutrient release by insect herbivores at non-outbreak levels in tropical forests than temperate and boreal forests, that these fluxes increase strongly with mean annual temperature, and that they exceed atmospheric deposition inputs in some localities. Thus, background levels of insect herbivory are sufficiently large to both alter ecosystem element cycling and influence terrestrial carbon cycling. Further, climate can affect interactions between natural populations of plants and herbivores with important consequences for global biogeochemical cycles across broadleaved forests.

Abstract Miombo woodlands are integral to livelihoods across southern Africa, biodiversity in the region, and the global carbon cycle, making accurate and precise monitoring of their state and change essential. Here, we assembled a terrestrial and airborne lidar dataset covering 50 kha of intact and degraded miombo woodlands, and generated aboveground biomass estimates with low uncertainty via direct 3D measurements of forest structure. We found 1.71 ± 0.09 TgC was stored in aboveground biomass across this landscape, between 1.5 and 2.2 times more than the 0.79–1.14 TgC estimated by conventional methods. This difference is in part owing to the systematic underestimation of large trees by allometry. If these results were extrapolated across Africa’s miombo woodlands, their carbon stock would potentially require an upward revision of approximately 3.7 PgC, implying we currently underestimate their carbon sequestration and emissions potential, and disincentivise their protection and restoration.

Heritage bridges constitute an integral feature of the urban landscape in numerous cities. However, it is common for these structures to surpass their life cycle, rendering them ill-equipped to withstand the dynamic demands of users and extreme events, particularly hydrological occurrences. This research presents a methodology for the assessment of heritage riverine bridges, with a focus on the Grau Bridge in Peru as a case study. The investigation commences with an exhaustive literature review, complemented by a historical examination, followed by a preliminary diagnosis. Subsequently, hydrological and hydraulic studies are presented, encompassing drone surveys of the riverbed and the bridge, soil analyses, and the application of 1D and 2D models in HEC-RAS. The outcomes of this comprehensive analysis reveal the high vulnerability of the Grau Bridge. Finally, strategic interventions for its conservation are recommended.

Water Distribution Networks are known to lose a consistent percentage of drinkable water due to the presence of leakages. In this paper it is proposed a solution to detect water leaks consisting of: i) a new sensing equipment able to acoustically monitor the external surface of a newly laid underground pipe; ii) a training of several machine learning models able to analyse the data collected by the new sensing equipment; iii) a user dashboard to give the final user the possibility to monitor the pipe’s condition. The research process included the generation of artificial leakages capable to produce a suitable dataset necessary to properly train machine learning models onto.

Abstract Recombinant multiepitope proteins (RMPs) are a promising alternative for application in diagnostic tests and, given their wide application in the most diverse diseases, this review article aims to survey the use of these antigens for diagnosis, as well as discuss the main points surrounding these antigens. RMPs usually consisting of linear, immunodominant, and phylogenetically conserved epitopes, has been applied in the experimental diagnosis of various human and animal diseases, such as leishmaniasis, brucellosis, cysticercosis, Chagas disease, hepatitis, leptospirosis, leprosy, filariasis, schistosomiasis, dengue, and COVID-19. The synthetic genes for these epitopes are joined to code a single RMP, either with spacers or fused, with different biochemical properties. The epitopes’ high density within the RMPs contributes to a high degree of sensitivity and specificity. The RMPs can also sidestep the need for multiple peptide synthesis or multiple recombinant proteins, reducing costs and enhancing the standardization conditions for immunoassays. Methods such as bioinformatics and circular dichroism have been widely applied in the development of new RMPs, helping to guide their construction and better understand their structure. Several RMPs have been expressed, mainly using the Escherichia coli expression system, highlighting the importance of these cells in the biotechnological field. In fact, technological advances in this area, offering a wide range of different strains to be used, make these cells the most widely used expression platform. RMPs have been experimentally used to diagnose a broad range of illnesses in the laboratory, suggesting they could also be useful for accurate diagnoses commercially. On this point, the RMP method offers a tempting substitute for the production of promising antigens used to assemble commercial diagnostic kits.

Hailstorms, while fascinating from a meteorological perspective, pose significant risks to communities, agriculture, and infrastructure. In regions such as the Central Andes of Peru, the characteristics and frequency of these extreme weather events remain largely uncharted. This study fills this gap by investigating the historical frequency and vertical structure of hailstorms in this region. We analyzed historical hailstorm records dating back to 1958 alongside 4 years of observations (2017–2021) from the Parsivel2 disdrometer and a cloud-profiling radar MIRA35c. Our findings indicate a trend of decreasing hail frequency (−0.5 events per decade). However, the p value of 0.07 suggests the need for further investigation, particularly in relation to environmental changes and reporting methods. The results show that hailstorms predominantly occur during the austral summer months, with peak frequency in December, and are most common during the afternoon and early evening hours. The analysis of radar variables such as reflectivity, radial velocity, spectral width, and linear depolarization ratio (LDR) reveals distinct vertical profiles for hail events. Two case studies highlight the diversity in the radar measurements of hailstorms, underscoring the complexity of accurate hail detection. This study suggests the need for refining the Parsivel2 algorithm and further understanding its classification of hydrometeors. Additionally, the limitations of conventional radar variables for hail detection are discussed, recommending the use of LDR and Doppler spectrum analysis for future research. Our findings lay the groundwork for the development of more efficient hail detection algorithms and improved understanding of hailstorms in the Central Andes of Peru.

Background Chagas disease (CD) is a neglected tropical disease endemic to Latin America, has emerged as a global health concern due to the migration of infected individuals. With its epidemiological complexity, by difficulty to obtain appropriate diagnoses and poor treatment, the search for novel therapeutic options remains. Methods In this context, we conducted a systematic review and meta-analysis of preclinical studies employing animal models to verify the progress in CD treatment. We searched the PubMed database for CD treatment studies published between 1990 and 2023, adhering to the PRISMA guidelines. Results Twelve papers met the inclusion criteria. The findings indicate that the fifteen treatment alternatives examined, mainly between 2010 and 2014, demonstrated efficacy in experimental CD models, evidenced by significant parasitemia reduction. Bis-triazole DO870 and VNI were effective in the acute and chronic phases, respectively. However, of these emerging therapies, only posaconazole and fexinidazole have progressed to clinical trials, yielding unsatisfactory outcomes as CD monotherapies Conclusions This meta-analysis highlights the existence of promising new drug candidates for CD treatment, but most remain in the preclinical stages. Those that reached clinical trials did not demonstrate optimal results, underscoring the ongoing challenges in CD therapy. Collaborative efforts among the academic community, pharmaceutical industries, funding agencies, and government agencies are urgently needed to accelerate the development of more effective medications against CD. Inplasy registration INPLASY202430101 (25/03/2024)

Abstract Methylmalonic acidemia cblB type (MMA cblB) is an autosomal recessive inborn error of amino acid metabolism that results in impaired synthesis of adenosylcobalamin, a cofactor of methylmalonyl‐CoA mutase. It presents with episodes of coma, vomiting, hypotonia, metabolic acidosis, and hyperammonemia. End‐stage kidney disease is a long‐term complication. Treatments include vitamin B12 supplementation, L‐carnitine, and a low‐protein diet. Liver, kidney, or combined liver‐kidney transplantations are promising options, but they are not without complications. We report a patient suffering from MMA cblB who developed end‐stage kidney disease at 18 years of age. Kidney transplantation allowed him to recover normal kidney function and good metabolic control. Unfortunately, after two decades, he developed non‐Hodgkin lymphoma and severe chemotherapy toxicity which led to his death. The risk of lymphoproliferative diseases is known to increase after solid organ transplantation. However, in MMA, factors including mitochondrial dysfunction and oncometabolites, may further increase the risk of malignancy and drug toxicity. Our report highlights the importance of considering the increased risk of cancer in long‐term follow‐up of MMA cblB patients, especially after solid organ transplantation. Moreover, when chemotherapy is needed, the increased risk of toxicity and metabolic decompensation should be considered and monitored.

Abstract To date, little is known about the usefulness of ultra-high frequency ultrasound (UHF-US, 50–70 MHz) in clinical practice for the diagnosis of dysimmune neuropathies. We present a prospective study aimed at comparing UHF-US alterations of nerves and fascicles in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), distal CIDP (d-CIDP) and anti-MAG neuropathy and their relationships with clinical and electrodiagnostic (EDX) features. 28 patients were included (twelve CIDP, 6 d-CIDP and 10 anti-MAG) and ten healthy controls. Each patient underwent neurological examination, EDX and UHF-US study of median and ulnar nerves bilaterally. UHF-US was reliable in differentiating immune neuropathies from controls when using mean and/or segmental nerve and/or fascicle cross-sectional area (CSA); furthermore, fascicle ratio (fascicle/nerve CSA) was a reliable factor for differentiating d-CIDP from other types of polyneuropathies. The fascicle CSA appears to be more increased in CIDP and its variant than in anti-MAG neuropathy. UHF-US offers information beyond simple nerve CSA and allows for a better characterization of the different forms of dysimmune neuropathies.

The primary purpose of this study was to investigate the impacts of the COVID-19 pandemic on demands, resources, and job satisfaction among a convenience sample of early childhood education (ECE) staff employed in Head Start preschools in a large metro area of Colorado. A survey was administered to a sample of Head Start staff at two timepoints: Time 1 (pre-COVID-19 pandemic) in October of 2019 (n = 137) and Time 2 (during the COVID-19 pandemic) in November of 2020 (n = 86). The survey consisted of a combination of validated measures to assess personal and external demands and resources and work satisfaction. Workload is a perceived external "demand" that significantly improved from pre- to mid-pandemic in this sample (z = -3.3, p < 0.01). Many personal and external "resources" changed pre- to mid-pandemic, though none were statistically significant. Overall job satisfaction in this sample increased, though it was not statistically significant (z = -1.04, p = 0.3). Mitigating demands, such as minimizing workload, and increasing job-related resources, such as bolstering management supports, may lead to improved job satisfaction of the ECE workforce employed in Head Start settings. Although the COVID-19 pandemic has amplified poor mental health and numerous job demands, some of the pandemic-related regulations may have also decreased the workload for some subgroups of the ECE workforce, potentially translating to improved job satisfaction. However, significant disparities remain with respect to personal and external demands among this sample of the ECE workforce compared to the national workforce suggesting multi-level resources and supports are critical to further buffer these stressors.

The purpose of this study was to (1) explore demands and resources among centre-based and Family, Friend and Neighbor (FFN) early childhood education (ECE) caregivers, and (2) investigate how these factors are associated with the quality of caregiver-child relationships. ECE caregivers (n = 257) completed a survey that assessed demands, resources, and the quality of caregiver-child relationships. Analyses included univariate and bivariate analyses and hierarchical linear regression modelling. Centre-based caregivers (n = 173) reported higher stress, less knowledge related to wellness, and lower confidence related to self-care practices compared to FFN caregivers (n = 84) (all p < 0.05). Mindfulness was associated with higher reported closeness with children in their care (p < 0.05). Centre-based caregivers may experience more demands and less resources compared to FFN caregivers which could impact the quality of care. Mindfulness strategies may help to mitigate demands and bolster the well-being of ECE caregivers and healthy early childhood development.

The present study aimed to extract polyphenolic compounds from lucuma (Pouteria lucuma) seeds using natural deep eutectic solvents (NADES) as a green, efficient, and environmentally friendly extraction. This was optimized by using the Response Surface Method (RSM) and comparing its predictive capacity with Artificial Neural Networks (ANN) and Convolutional Neural Networks (CNN). Four NADES were prepared by mixing lactic acid (LA) with each of the following reagents: sodium acetate (SA), urea (U), glucose (G), and ammonium acetate (AA), separately. The yield of total phenolic compounds (TPC) obtained from lucuma seeds with each NADES was measured as an optimization criterion with the Box-Benhken design. The following factors were evaluated: time, temperature, and the lucuma seed flour (LSF): NADES ratio. The response variables were TPC and antioxidant activity. The LA-AA extract was selected because it exhibited the highest TPC value and was analyzed by UHPLC–MS (Ultra-performance Liquid Chromatography-Mass Spectrometry). From the RSM, the optimal extraction parameters were 80 min, 52°C, and LSF: NADES ratio of 8:100 (w/v), obtaining a TPC value of 3601.51 ± 0.51 mg GAE/100 g LFS. UHPLC–MS analysis evidenced the formation of epigallocatechin isomers from epigallocatechin gallate. The predictive ability of ANNs compared to RSM was demonstrated.