Acyl-CoA-binding protein (ACBP), also known as diazepam binding inhibitor (DBI), is a small phylogenetically conserved protein. This ancestral peptide is multifunctional, performing intracellular ...activities as ACBP protein or extracellular roles as DBI. Several studies showed its endless facets, including a relevant activity as appetite stimulator and as anabolic factor. High levels of ACBP have been described in erythrocytes, liver, kidney, and gut cells. The aim of this study was to analyze, at immunohistochemical level, the expression of ACBP in fetal human tissues during development, focusing on the developing kidney.
Immunohistochemistry for ACBP was performed on 30 human fetal kidneys, from 15 fetuses of gestational age ranging from 13 to 19 weeks. At autopsy, all kidney samples were 10% formalin-fixed, routinely processed and paraffin-embedded. Five micron-thick paraffin sections were stained with Hematoxylin and Eosin and PAS stain for a morphological examination.
ACBP was detected in all 30 kidneys analyzed in this study. No significant changes in ACBP expression were observed at different gestational ages. Immunostaining for ACBP was restricted to the epithelium covering the renal pelvis, the papillae, the collecting tubules, and the proximal and distal tubules. On the other hand, medullary regions and in the metanephric mesenchymal stem/progenitor cells did not show any reactivity for ACBP.
According to our findings, ACBP should be considered as a new player in the complex field of human nephrogenesis, given that it was detected in all fetal kidneys immunostained. Its preferential localization in the renal structures derived from the Wolf duct, such as pelvis epithelium and collecting ducts, suggests a major role for ACBP in the induction of the metanephric mesenchymal cells toward the differentiation into glomerular structures. ACBP expression in proximal and distal tubules, two structures originating from the metanephric mesenchyme, indicates a further role of this protein in nephron development. In conclusion, ACBP should be added to the multiple molecules involved in human nephrogenesis.
We estimated glomerular cell number in 50 normotensive type 1 diabetic patients with raised albumin excretion rate (AER) and investigated any change after 3 years in a subgroup of 16 placebo-treated ...patients. Biopsies from 10 normal kidney donors were used as controls. Mesangial and endothelial cell number was increased in the 50 diabetic patients at the start of the study compared with control subjects. There was no difference in podocyte number. Glomerular volume was increased in diabetic patients, but surface area of glomerular basement membrane (GBM) underlying the podocytes did not differ between groups. AER correlated positively with mesangial cell number in microalbuminuric patients (r = 0.44, P = 0.012) and negatively with podocyte number in proteinuric patients (r = -0.48, P = 0.040). In the 16 placebo-treated patients, glomerular volume increased after 3 years owing to matrix accumulation and increased GBM surface area. Although overall cell number did not differ significantly from baseline, the decrease in podocyte number during follow-up correlated with AER at follow-up (r = -0.72, P = 0.002). In conclusion, cross-sectional analysis of podocyte number in type 1 diabetic patients with raised AER but normal blood pressure shows no significant reduction compared with nondiabetic control subjects. Longitudinal data provide evidence for an association between podocyte loss and AER, but whether cellular changes are a response to, a cause of, or concomitant with the progression of nephropathy remains uncertain.
This study presents a novel approach specifically designed for real-world driving scenarios of heavy-duty fuel cell vehicles, named P-ECMS. The P-ECMS addresses both charge-sustaining and ...charge-depleting modes of the battery to optimize the vehicle’s energy management. To this aim, the P-ECMS integrates a velocity prediction layer and a SOC planning layer. The velocity prediction layer utilizes a realistic driving dataset obtained from GT-Real Drive, using information from the TEN-T routes, to accurately predict the speed of the vehicle. The SOC planning layer, leveraging information from a map service provider, plans a target SOC trajectory at the beginning of the driving mission. It employs a neural network trained on the policy obtained from a standard optimized ECMS for various driving cycles and initial SOC values, aiming to achieve a final SOC of 30%. In charge-sustaining operations, the P-ECMS is compared to a conventional Adaptive-ECMS, the reference ECMS (Standard-ECMS), and a rule-based strategy across the HDDT driving cycle. The evaluation focuses on battery SOC sustenance, equivalence factor evolution, and hydrogen consumption. Results show that both the P-ECMS and the A-ECMS outperform the S-ECMS in terms of SOC sustenance, with the P-ECMS achieving a significant 2% reduction in hydrogen consumption compared to the A-ECMS. The study demonstrates that the P-ECMS advantages extend to battery discharge conditions, as it achieves a remarkable reduction in consumption compared to an optimal Charge-Depleting/Charge-Sustaining (up to 5%) when employing a linear battery discharge planning. The integration of the SOC planning layer proves additional benefits, and a comparison between the P-ECMS with linear battery discharge planning and the P-ECMS with the SOC planning layer integrated shows the advantages of SOC trajectory planning for different segment lengths. The study suggests an optimal segment length between 3 km and 8 km, obtained with the necessary data from a map service provider.
•Research on a predictive energy management strategy for heavy-duty fuel cell vehicles.•Development and testing of NN-based optimal battery SOC planner integrated into the P-ECMS.•P-ECMS combines velocity prediction and SOC planning for efficient energy utilization.•Evaluation of the hydrogen consumption for heavy-duty fuel cell vehicle in real driving.•P-ECMS achieves up to 5% consumption reduction compared to optimal Charge-Depleting/Charge-Sustaining.
Background
Atopic dermatitis (AD) is a common inflammatory skin disease that affects both children and adults. However, limited research has been conducted on gender differences in AD.
Objectives
...This study aimed to assess gender differences in adult AD patients, focusing on demographic and clinical features, comorbidities and treatment approaches.
Methods
In this multicentre, observational, cross‐sectional study, we enrolled 686 adult patients with AD (357 males and 329 females). For each patient, we collected demographic data (age and sex), anthropometric measurements (weight, height, hip circumference, waist circumference and waist‐to‐hip ratio), clinical information (onset age, disease duration, severity, itching intensity, impact on quality of life) and noted comorbidities (metabolic, atopic and other). We recorded past and current topical and systemic treatments. We analysed all collected data using statistical techniques appropriate for both quantitative and qualitative variables. Multiple correspondence analysis (MCA) was employed to evaluate the relationships among all clinical characteristics of the patients.
Results
We found no differences in age at onset, disease duration, severity and quality of life impact between males and females. Males exhibited higher rates of hypertriglyceridaemia and hypertension. No significant gender differences were observed in atopic or other comorbidities. Treatment approaches were overlapping, except for greater methotrexate use in males. MCA revealed distinct patterns based on gender, disease severity, age of onset, treatment and quality of life. Adult males with AD had severe disease, extensive treatments and poorer quality of life, while adult females had milder disease, fewer treatments and moderate quality of life impact.
Conclusions
Our study reveals that gender differences in adult AD patients are largely due to inherent population variations rather than disease‐related disparities. However, it highlights potential undertreatment of females with moderate AD and quality of life impact, emphasizing the need for equitable AD treatment. JAK inhibitors may offer a solution for gender‐based therapeutic parity.
A multicentre observational study was aimed to assess the prevalence of late-onset Pompe disease (LOPD) in a large high-risk population, using the dried blood spot (DBS) as a main screening tool.
17 ...Italian neuromuscular centres were involved in the late-onset Pompe early diagnosis (LOPED) study. Inclusion criteria were: (1) age ≥5 years, (2) persistent hyperCKaemia and (3) muscle weakness at upper and/or lower limbs (limb-girdle muscle weakness, LGMW). Acid α-glucosidase (GAA) activity was measured separately on DBS by fluorometric as well as tandem mass spectrometry methods. A DBS retest was performed in patients resulted positive at first assay. For the final diagnosis, GAA deficiency was confirmed by a biochemical assay in skeletal muscle, whereas genotype was assessed by GAA molecular analysis.
In a 14-month period, we studied 1051 cases: 30 positive samples (2.9%) were detected by first DBS screening, whereas, after retesting, 21 samples were still positive. Biochemical and molecular genetic studies finally confirmed LOPD diagnosis in 17 cases (1.6%). The median time from the onset of symptoms/signs to diagnosis was 5 years. Among those patients, 35% showed presymptomatic hyperCKaemia and 59% showed hyperCKaemia+LGMW, whereas 6% manifested with LGMW.
LOPED study suggests that GAA activity should be accurately screened by DBS in all patients referring for isolated hyperCKaemia and/or LGMW. A timely diagnosis was performed in five patients with presymptomatic hyperCKaemia, but two had already manifested with relevant changes on muscle morphology and MRI. Consequently, enzyme replacement therapy was started in 14/17 patients, including the 2 patients still clinically presymptomatic but with a laboratory evidence of disease progression.
Genetic studies of complex traits have mainly identified associations with noncoding variants. To further determine the contribution of regulatory variation, we combined whole-genome and ...transcriptome data for 624 individuals from Sardinia to identify common and rare variants that influence gene expression and splicing. We identified 21,183 expression quantitative trait loci (eQTLs) and 6,768 splicing quantitative trait loci (sQTLs), including 619 new QTLs. We identified high-frequency QTLs and found evidence of selection near genes involved in malarial resistance and increased multiple sclerosis risk, reflecting the epidemiological history of Sardinia. Using family relationships, we identified 809 segregating expression outliers (median z score of 2.97), averaging 13.3 genes per individual. Outlier genes were enriched for proximal rare variants, providing a new approach to study large-effect regulatory variants and their relevance to traits. Our results provide insight into the effects of regulatory variants and their relationship to population history and individual genetic risk.
At the present time, gut microbiota inspires great interest in the field of neuroscience as a function of its role in normal physiology and involvement in brain function. This aspect suggests a ...specific gut-brain pathway, mainly modulated by gut microbiota activity. Among the multiple actions controlled by microbiota at the brain level, neuronal plasticity and cognitive function represent two of the most interesting aspects of this cross-talk communication. We address the possible action of two-months implementation of gut Bifidobacteria using a mixture of three different strains (B-MIX) on hippocampal plasticity and related cognitive behavior in adult healthy Sprague Dawley rats. B-MIX treatment increases the hippocampal BDNF with a parallel gain in dendritic spines’ density of hippocampal CA1 pyramidal neurons. Electrophysiological experiments revealed a significant increment of HFS-induced LTP formation on the CA1 hippocampal region in B-MIX treated rats. All these effects are accompanied by a better cognitive performance observed in B-MIX treated animals with no impairments in locomotion activity. Therefore, in adult rats, the treatment with different strains of bifidobacteria is able to markedly enhance neuronal plasticity and the CNS function influencing cognitive behavior, an effect that may suggest a potential therapeutic treatment in brain diseases associated with cognitive functions.
•Treatment Bifidobacteria in healthy rats increases the hippocampal neuronal plasticity.•The treatment improves cognitive behavior.•The treatment increases in the content of hippocampal BDNF with a parallel rise in dendritic spines density and neuronal growth.
We present deep polarimetric observations of the European Large Area ISO Survey-North 1 (ELAIS-N1) field using the Low Frequency Array (LOFAR) at 114.9–177.4 MHz. The ELAIS-N1 field is part of the ...LOFAR Two-metre Sky Survey deep fields data release I. For six eight-hour observing epochs, we align the polarization angles and stack the 20″-resolution Stokes
Q
,
U
-parameter data cubes. This produces a 16 deg
2
image with 1
σ
QU
sensitivity of 26
μ
Jy beam
−1
in the central area. In this paper, we demonstrate the feasibility of the stacking technique, and we generate a catalog of polarized sources in ELAIS-N1 and their associated Faraday rotation measures (RMs). While in a single-epoch observation we detect three polarized sources, this number increases by a factor of about three when we consider the stacked data, with a total of ten sources. This yields a surface density of polarized sources of one per 1.6 deg
2
. The Stokes
I
images of three of the ten detected polarized sources have morphologies resembling those of FR I radio galaxies. This represents a greater fraction of this type of source than previously found, which suggests that more sensitive observations may help with their detection.
Astrocytes represent the most abundant cell type in the brain, where they play critical roles in synaptic transmission, cognition, and behavior. Recent discoveries show astrocytes are involved in ...synaptic dysfunction during Alzheimer's disease (AD). AD patients have imbalanced cholesterol metabolism, demonstrated by high levels of side-chain oxidized cholesterol known as 27-hydroxycholesterol (27-OH). Evidence from our laboratory has shown that elevated 27-OH can abolish synaptic connectivity during neuromaturation, but its effect on astrocyte function is currently unclear. Our results suggest that elevated 27-OH decreases the astrocyte function
in Cyp27Tg, a mouse model of brain oxysterol imbalance. Here, we report a downregulation of glutamate transporters in the hippocampus of CYP27Tg mice together with increased GFAP. GLT-1 downregulation was also observed when WT mice were fed with high-cholesterol diets. To study the relationship between astrocytes and neurons, we have developed a 3D co-culture system that allows all the cell types from mice embryos to differentiate
. We report that our 3D co-cultures reproduce the effects of 27-OH observed in 2D neurons and
. Moreover, we found novel degenerative effects in astrocytes that do not appear in 2D cultures, together with the downregulation of glutamate transporters GLT-1 and GLAST. We propose that this transporter dysregulation leads to neuronal hyperexcitability and synaptic dysfunction based on the effects of 27-OH on astrocytes. Taken together, these results report a new mechanism linking oxysterol imbalance in the brain and synaptic dysfunction through effects on astrocyte function.
We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the ...genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the γ-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G
>
C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the ɛ4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.
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