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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.

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.

The primary climatic characteristic of olive cultivation in Peru is the coastal desert environment with moderate temperatures, minimal precipitation, and high atmospheric water content during the winter season. This report presents a comprehensive study on water and carbon fluxes in a drip-irrigated olive orchard in Pisco Province, Peru, addressing the current lack of information on olive physiology and water management under these environmental conditions. The eddy covariance system installed in September 2019 showed an average ET of 2.18 ± 0.38 mm d−1, with seasonal variation. Drip irrigation was set at 60 m3 ha−1 d−1 during the growing season and reduced to half that amount in the winter. The study suggests that using deficit irrigation based on affordable dendrometry sensors could reduce water use by close to 30% while potentially preserving biomass gain and fruit yields. This could help improve water management in olive cultivation in coastal Peru.

Visceral Leishmaniasis (VL) is a serious public health issue, documented in more than ninety countries, where an estimated 500,000 new cases emerge each year. Regardless of novel methodologies, advancements, and experimental interventions, therapeutic limitations, and drug resistance are still challenging. For this reason, based on previous research, we screened natural products (NP) from Nuclei of Bioassays, Ecophysiology, and Biosynthesis of Natural Products Database (NuBBEDB), Mexican Compound Database of Natural Products (BIOFACQUIM), and Peruvian Natural Products Database (PeruNPDB) databases, in addition to structural analogs of Miglitol and Acarbose, which have been suggested as treatments for VL and have shown encouraging action against parasite’s N-glycan biosynthesis. Using computer-aided drug design (CADD) approaches, the potential inhibitory effect of these NP candidates was evaluated by inhibiting the Mannosyl-oligosaccharide Glucosidase Protein (MOGS) from Leishmania infantum, an enzyme essential for the protein glycosylation process, at various pH to mimic the parasite’s changing environment. Also, computational analysis was used to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profile, while molecular dynamic simulations were used to gather information on the interactions between these ligands and the protein target. Our findings indicated that Ocotillone and Subsessiline have potential antileishmanial effects at pH 5 and 7, respectively, due to their high binding affinity to MOGS and interactions in the active center. Furthermore, these compounds were non-toxic and had the potential to be administered orally. This research indicates the promising anti-leishmanial activity of Ocotillone and Subsessiline, suggesting further validation through in vitro and in vivo experiments.

Introducción: estudios previos informaron un aumento de los debuts de diabetes mellitus tipo 1 (DM1) en niños residentes de las regiones gravemente afectadas por la pandemia de COVID-19. Objetivos: determinar las tasas y la severidad de los debuts por DM1 en poblaciones pediátricas de varios centros argentinos durante la pandemia de COVID-19 durante el confinamiento de 2020, y compararlos con la prepandemia (2018-2019) y la pospandemia (2021-2022). Materiales y métodos: revisión retrospectiva de historias clínicas donde se determinaron las tasas de debuts de DM1 en niños de 6 meses a 16 años durante el confinamiento (2020), la prepandemia (2018 y 2019) y la pospandemia (2021-2022) en 28 centros argentinos. Para determinar la tasa de debuts de DM1, se dividió el número de debuts de DM1 por año por la población proyectada. Resultados: se incluyeron 1997 casos (48,5% mujeres), el 50,1% tenía obra social. Los valores medios ± un desvío estándar fueron: edad 8,7±3,7 años, glucosa 468±184 mg/dL, HbA1c 11,3% ±2,5, pH 7,21±0,2 y bicarbonato 13,4±7,7. No hubo diferencias significativas en la edad, índice de masa corporal (IMC), glucosa y HbA1c entre 2018 y 2022. Sin embargo, el pH (7,19 versus 7,23) y el bicarbonato (12,5 versus 14,7 mEq/L) fueron significativamente más bajos en 2020 versus 2018. La tasa de debuts de DM1 por 100.000 habitantes fue mayor en 2020 (3,5) versus la prepandemia: 2,9 en 2018 y 3,2 en 2019. No obstante, durante 2021 y 2022 las tasas de DM1 fueron incluso superiores a la de 2020, con 4,4 y 4,0, respectivamente. Conclusiones: se ha registrado un aumento de debuts de DM1 en diferentes centros médicos de Argentina desde la pandemia. Los niveles de bicarbonato y pH de los debuts de DM1 fueron significativamente más bajos durante el confinamiento por la pandemia (2020) comparados con la prepandemia (2018).

Abstract Background Zellweger spectrum disorders (ZSD) and X-linked adrenoleukodystrophy (X-ALD) are inherited metabolic diseases characterized by dysfunction of peroxisomes, that are essential for lipid metabolism and redox balance. Oxidative stress has been reported to have a significant role in the pathogenesis of neurodegenerative diseases such as peroxisomal disorders, but little is known on the intracellular activation of Mitogen-activated protein kinases (MAPKs). Strictly related to oxidative stress, a correct autophagic machinery is essential to eliminated oxidized proteins and damaged organelles. The aims of the current study are to investigate a possible implication of MAPK pathways and autophagy impairment as markers and putative therapeutic targets in X-ALD and ZSDs. Methods Three patients with ZSD (2 M, 1 F; age range 8–17 years) and five patients with X-ALD (5 M; age range 5- 22 years) were enrolled. A control group included 6 healthy volunteers. To evaluate MAPKs pathway, p-p38 and p-JNK were assessed by western blot analysis on peripheral blood mononuclear cells. LC3II/LC3I ratio was evaluated ad marker of autophagy. Results X-ALD and ZSD patients showed elevated p-p38 values on average 2- fold (range 1.21- 2.84) and 3.30-fold (range 1.56- 4.26) higher when compared with controls, respectively. p-JNK expression was on average 12-fold (range 2.20–19.92) and 2.90-fold (range 1.43–4.24) higher in ZSD and X-ALD patients than in controls. All patients had altered autophagic flux as concluded from the reduced LC3II/I ratio. Conclusions In our study X-ALD and ZSD patients present an overactivation of MAPK pathways and an inhibition of autophagy. Considering the absence of successful therapies and the growing interest towards new therapies with antioxidants and autophagy inducers, the identification and validation of biomarkers to monitor optimal dosing and biological efficacy of the treatments is of prime interest.

This analysis compares the energy efficiency and operational costs of combustion vehicles (Hyundai Accent 1.6 L and Chevrolet Sail 1.5 L) with the Nissan Leaf, an electric vehicle, under current fuel and electricity pricing in Ecuador. Combustion vehicles, converting gasoline into mechanical energy, demonstrate substantial energy losses, leading to higher operational costs, especially with recent gasoline price hikes to USD 2.722 per gallon. In stark contrast, the Nissan Leaf exhibits significantly greater energy efficiency, consuming only 15–20 kWh per 100 km, which translates to lower running costs (USD 11.20 to fully charge a 40 kWh battery). Despite the clear economic and environmental benefits of electric vehicles, their adoption in Ecuador is hampered by geographical challenges such as diverse terrain that can affect vehicle range and battery longevity. Moreover, the limited and uneven distribution of EV charging stations, mostly concentrated in urban areas, poses significant barriers. For broader implementation, a strategic expansion of the EV infrastructure and careful consideration of the national energy grid’s capacity to support increased electric vehicle uptake are essential. Addressing these challenges is crucial for realizing the full potential of electric vehicles in enhancing Ecuador’s sustainability and energy independence.

This paper introduces an innovative approach to address the distribution network reconfiguration (DNR) challenge, aiming to reduce power loss through an advanced hyperbolic tangent particle swarm optimization (HT-PSO) method. This approach is distinguished by the adoption of a novel hyperbolic tangent function, which effectively limits the rate of change values, offering a significant improvement over traditional sigmoid function-based methods. A key feature of this new approach is the integration of a tunable parameter, δ, into the HT-PSO, enhancing the curve’s adaptability. The careful optimization of δ ensures superior control over the rate of change across the entire operational range. This enhanced control mechanism substantially improves the efficiency of the search and convergence processes in DNR. Comparative simulations conducted on 33- and 94-bus systems show an improvement in convergence, demonstrating a more exhaustive exploration of the search space than existing methods documented in the literature based on PSO and variations where functions are proposed for the rate of change of values.