Several homeoprotein transcription factors transfer between cells and regulate gene expression, protein translation, and chromatin organization in recipient cells. ENGRAILED‐1 is one such ...homeoprotein expressed in spinal V1 interneurons that synapse on α‐motoneurons. Neutralizing extracellular ENGRAILED‐1 by expressing a secreted single‐chain antibody blocks its capture by spinal motoneurons resulting in α‐motoneuron loss and limb weakness. A similar but stronger phenotype is observed in the Engrailed‐1 heterozygote mouse, confirming that ENGRAILED‐1 exerts a paracrine neurotrophic activity on spinal cord α‐motoneurons. Intrathecal injection of ENGRAILED‐1 leads to its specific internalization by spinal motoneurons and has long‐lasting protective effects against neurodegeneration and weakness. Midbrain dopaminergic neurons express Engrailed‐1 and, similarly to spinal cord α‐motoneurons, degenerate in the heterozygote. We identify genes expressed in spinal cord motoneurons whose expression changes in mouse Engrailed‐1 heterozygote midbrain neurons. Among these, p62/SQSTM1 shows increased expression during aging in spinal cord motoneurons in the Engrailed‐1 heterozygote and upon extracellular ENGRAILED‐1 neutralization. We conclude that ENGRAILED‐1 might regulate motoneuron aging and has non‐cell‐autonomous neurotrophic activity.
Synopsis
Reducing ENGRAILED‐1 expression in V1 interneurons of the ventral spinal cord or blocking its transfer from interneurons to motoneurons leads to α‐motoneuron retrograde degeneration. Exogenous ENGRAILED‐1 addressed to motoneurons restores a wild‐type phenotype in ENGRAILED‐1 heterozygotes.
ENGRAILED‐1 secreted by V1 interneurons or intrathecally injected is specifically internalized by motoneurons.
Reducing ENGRAILED‐1 internalization induces α-motoneurons degeneration.
Intrathecally injected ENGRAILED‐1 restores a long‐lasting wild‐type phenotype in ENGRAILED‐1 heterozygotes.
Reducing ENGRAILED‐1 expression in V1 interneurons of the ventral spinal cord or blocking its transfer from interneurons to motoneurons leads to α‐motoneuron retrograde degeneration. Exogenous ENGRAILED‐1 addressed to motoneurons restores a wild‐type phenotype in ENGRAILED‐1 heterozygotes.
The total synthesis of Laetevirenol A, a natural product with antioxidant activity, has been achieved. A gold‐catalyzed cycloisomerization of an o‐alkenyl‐o’‐alkynylbiphenyl has been used as the key ...step for the construction of the phenanthrene moiety present in Laetevirenol A. Several studies in model substrates have been carried out to unveil the effect of substituents in different locations in the outcome of this cyclization, which allowed the design of an appropriate precursor for the fundamental gold‐catalyzed cycloisomerization. The suitably functionalized phenanthrene intermediate obtained in this key step could be further transformed into Laetevirenol A via a Friedel‐Crafts cyclization, which also turned out to be dependent on the nature of the substituents. Finally, Laetevirenol A was obtained in 10 steps from commercially available substrates, with a 20% global yield.
Proteins, especially plant proteins, may reduce inflammation among adults with chronic kidney disease (CKD). This systematic review and meta-analysis were conducted to evaluate the effect protein ...types (animal or plant) have on inflammation markers (CRP, IL-6, TNF-α) among adults with varying stages of CKD. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was conducted to identify articles from inception until January 2021, utilizing six databases. Controlled trials that compared the effects of different protein types were analyzed using random-effects meta-analysis. Quality assessment and risk of bias of the included articles were assessed by using Cochrane risk of bias instrument and ROBINS-I. Out of the 10 studies that met the criteria, there was a decreasing trend in CRP levels when consuming plant proteins compared to animal proteins among non-dialysis participants. There was a statistically significant decrease when comparing animal proteins to unspecified proteins in CRP levels among dialysis participants Hedges’ g = 2.11; 95% CI 1.12, 3.11; p ≤ 0.001, favoring unspecified proteins. Furthermore, animal proteins (eggs, red meat) showed increasing trends in CRP levels compared to whey protein isolate. Caution must be considered regarding these results as controlled, non-randomized, trials were included in the analysis, which may have contributed to high risk of bias. Future research should focus on protein types and the impact they have on kidney disease progression and inflammation markers.
The adaptation of adenoviruses as gene delivery tools has resulted in the development of high-capacity adenoviral vectors (HC-AdVs), also known, helper-dependent or "gutless". Compared with earlier ...generations (E1/E3-deleted vectors), HC-AdVs retain relevant features such as genetic stability, remarkable efficacy of in vivo transduction, and production at high titers. More importantly, the lack of viral coding sequences in the genomes of HC-AdVs extends the cloning capacity up to 37 Kb, and allows long-term episomal persistence of transgenes in non-dividing cells. These properties open a wide repertoire of therapeutic opportunities in the fields of gene supplementation and gene correction, which have been explored at the preclinical level over the past two decades. During this time, production methods have been optimized to obtain the yield, purity, and reliability required for clinical implementation. Better understanding of inflammatory responses and the implementation of methods to control them have increased the safety of these vectors. We will review the most significant achievements that are turning an interesting research tool into a sound vector platform, which could contribute to overcome current limitations in the gene therapy field.
This article presents a study, intending to design a model with 90% reliability, which helps in the prediction of school dropouts in higher and secondary education institutions, implementing machine ...learning techniques. The collection of information was carried out with open data from the 2015 Intercensal Survey and the 2010 and 2020 Population and Housing censuses carried out by the National Institute of Statistics and Geography, which contain information about the inhabitants and homes. in the 32 federal entities of Mexico. The data were homologated and twenty variables were selected, based on the correlation. After cleaning the data, there was a sample of 1,080,782 records in total. Supervised learning was used to create the model, automating data processing with training and testing, applying the following techniques, Artificial Neural Networks, Support Vector Machines, Linear Ridge and Lasso Regression, Bayesian Optimization, Random Forest, the first two with a reliability greater than 99% and the last with 91%.
In the opposite direction, family networks (e.g. secondary caregivers) that provide support to people with dementia are decreasing in size, something that contributes to an increase in the demands ...and burden that is usually faced by primary family caregivers, most of whom are female. Even when dementia plays an important role in the explanation of the occurrence of the BPSD, it is well known that other factors from the environment (social and physical), the caregiver (informal or formal), and the family play a decisive role in understanding why BPSD happen (Kales etal., 2015; Losada Baltar etal., 2017), as well as their frequency and associated distress for caregivers. ...even though there are many examples of intervention studies that have shown at least a moderate efficacy for reducing caregivers’ distress (Cheng etal., 2020) and negative outcomes on care-recipients (Spector etal., 2013; Strøm etal., 2016), the truth is that there is a clear frontier between the scientific context in which these interventions are developed and tested and the availability of evidence-based therapies in the applied, real-world context.
Abstract
Nitrogen-fixing cyanobacteria from the order Nostocales are able to establish symbiotic relationships with diverse plant species. They are promiscuous symbionts, as the same strain of ...cyanobacterium is able to form symbiotic biological nitrogen-fixing relationships with different plants species. This review will focus on the different types of cyanobacterial–plant associations, both endophytic and epiphytic, and provide insights from a structural viewpoint, as well as our current understanding of the mechanisms involved in the symbiotic crosstalk. In all these symbioses, the benefit for the plant is clear; it obtains from the cyanobacterium fixed nitrogen and other bioactive compounds, such as phytohormones, polysaccharides, siderophores, or vitamins, leading to enhanced plant growth and productivity. Additionally, there is increasing use of different cyanobacterial species as bio-inoculants for biological nitrogen fixation to improve soil fertility and crop production, thus providing an eco-friendly, alternative, and sustainable approach to reduce the over-reliance on synthetic chemical fertilizers.
Improved understanding of cyanobacteria–plant symbiosis for biological nitrogen fixation, and deciphering the molecular mechanisms that underpin these interactions has the potential to inform strategies for reducing environmental footprints in agriculture.
Various levels of lockdown due to COVID-19 limit people’s habitual physical activity. Individuals addicted to exercise, health-oriented, and team-exercisers could be the most affected. We examined ...the COVID-19-related changes in exercise volume in 1079 exercisers from eight Spanish-speaking nations based on exercise addiction categories, primary reasons for exercise, and forms of exercise. The COVID-19-related decrease in exercise volume was 49.24% in the sample. The proportion of the risk of exercise addiction was 15.2%. Most (81.7%) of the participants exercised for a health-related reason. These exercisers reported lesser decrease in their exercise volume than those exercising for social reasons. The risk of exercise addiction was inversely related to changes in exercise volume, but after controlling for passion and perfectionism the relationship vanished. The reported effect of COVID-19 on training did not differ between the exercise addiction groups. The findings also confirm that exercise addiction research should control for passion and perfectionism.
In Ecuador, the number of adults on hemodialysis (HD) continues to rise. Currently, the effect dietary habits and socioeconomic status (SES) have on blood pressure is not known for those on HD.
The ...objectives of this study focused on adults on HD in Quito, Ecuador to
) assess the relationship between dietary intake and SES;
) compare dietary intake to the Kidney Disease Outcomes Quality Initiative (KDOQI) guidelines; and
) explore the relationship between dietary intake and systolic blood pressure.
This cross-sectional study was conducted at the dialysis center within Eugenio Espejo Specialties Hospital in Quito, Ecuador between May and June 2022 among 50 adults on HD. Three 24-h recalls were used to determine average dietary intake and the 25-item Instituto Nacional de Estadística y Censos-Stratification of SES was used to determine SES. Electrolytes and 2 blood pressure readings were collected. Qualitative narrative data analysis was performed to identify themes using NVivo v12. T-tests of independence, simple, and multiple linear regressions using age and sex as confounders were conducted using R and a
0.05 was deemed as statistically significant.
On an average, 76% of participants consumed <25 kcal/kg body weight energy and 64% consumed <1 g protein/kg body weight. Participants consumed less energy and protein compared with the KDOQI guidelines (
0.05). Positive relationships were observed with potassium and blood pressure (β = 0.020,
0.05) and SES with energy, protein, and phosphorus (
0.05). Themes that were identified as contributing to dietary intake were limited knowledge, lack of consistency with dietary information, and limited appetite.
Findings from this study indicate that the focus should be on improving energy and protein intake for this population.
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