Search

Abstract IP3 receptor (IP3R)-mediated Ca2+ transfer at the mitochondria-endoplasmic reticulum (ER) contact sites (MERCS) drives mitochondrial Ca2+ uptake and oxidative metabolism and is linked to different pathologies, including Parkinson’s disease (PD). The dependence of Ca2+ transfer efficiency on the ER-mitochondria distance remains unexplored. Employing molecular rulers that stabilize ER-mitochondrial distances at 5 nm resolution, and using genetically encoded Ca2+ indicators targeting the ER lumen and the sub-mitochondrial compartments, we now show that a distance of ~20 nm is optimal for Ca2+ transfer and mitochondrial oxidative metabolism due to enrichment of IP3R at MERCS. In human iPSC-derived astrocytes from PD patients, 20 nm MERCS were specifically reduced, which correlated with a reduction of mitochondrial Ca2+ uptake. Stabilization of the ER-mitochondrial interaction at 20 nm, but not at 10 nm, fully rescued mitochondrial Ca2+ uptake in PD astrocytes. Our work determines with precision the optimal distance for Ca2+ flux between ER and mitochondria and suggests a new paradigm for fine control over mitochondrial function.

Background: Aldosterone synthase (CYP11B2) is crucial for aldosterone production, and variations in its gene may influence type 2 diabetes mellitus (T2DM) development. This study explores the link between two single nucleotide polymorphisms (SNPs) in the CYP11B2 gene - −344T/C and K173R and T2DM in the Moroccan population .

Introduction: Osteoarthritis (OA), a chronic inflammatory joint disorder, still lacks effective therapeutic interventions. Consequently, the development of convenient experimental models is crucial. Recently, research has focused on the plasticity of Mesenchymal Stem/stromal Cells, particularly adipose-derived ones (ASCs), in halting OA progression. This study investigates the therapeutic potential of a cell-free approach, ASC-derived conditioned medium (CM), in reversing cytokine-induced OA markers in an ex vivo model of human cartilage explants. Methods: 4 mm cartilage punches, derived from the femoral heads of patients undergoing total hip replacement, were treated with 10 ng/ml TNFα, 1 ng/ml IL-1β, or a combination of both, over a 3-day period. Analysis of OA-related markers, such as MMP activity, the release of NO and GAGs, and the expression of PTGS2, allowed for the selection of the most effective inflammatory stimulus. Subsequently, explants challenged with TNFα+IL-1β were exposed to CM, consisting of a pool of concentrated supernatants from 72-h cultured ASCs, in order to evaluate its effect on cartilage catabolism and inflammation. Results: The 3-day treatment with both 10ng/ml TNFα and 1ng/ml IL-1β significantly increased MMP activity and NO release, without affecting GAG release. The addition of CM significantly downregulated the abnormal MMP activity induced by the inflammatory stimuli, while also mildly reducing MMP3, MMP13, and PTGS2 gene expression. Finally, SOX9 and COL2A1 were downregulated by the cytokines, and further decreased by CM. Conclusion: The proposed cartilage explant model offers encouraging evidence of the therapeutic potential of ASC-derived CM against OA, and it could serve as a convenient ex vivo platform for drug screening.

Abstract The paper analyzes the cryptocurrency ecosystem at both the aggregate and individual levels to understand the factors that impact future volatility. The study uses high-frequency panel data from 2020 to 2022 to examine the relationship between several market volatility drivers, such as daily leverage, signed volatility and jumps. Several known autoregressive model specifications are estimated over different market regimes, and results are compared to equity data as a reference benchmark of a more mature asset class. The panel estimations show that the positive market returns at the high-frequency level increase price volatility, contrary to what is expected from the classical financial literature. We attributed this effect to the price dynamics over the last year of the dataset (2022) by repeating the estimation on different time spans. Moreover, the positive signed volatility and negative daily leverage positively impact the cryptocurrencies’ future volatility, unlike what emerges from the same study on a cross-section of stocks. This result signals a structural difference in a nascent cryptocurrency market that has to mature yet. Further individual-level analysis confirms the findings of the panel analysis and highlights that these effects are statistically significant and commonly shared among many components in the selected universe.

The Winged Victory (Vittoria Alata) of Brescia is one of the most important Roman bronzes in Italy. Discovered in 1826, it dates back to the 1st century AD. Since the 19th century the statue has undergone multiple conservation interventions. The last one started in 2018 up to 2020. The project was defined with a multidisciplinary approach which made it possible to study and compare the data obtained from the restoration with those deriving from scientific analyses, humanistic studies and other specialist research. For the first time after the discovery, it was possible to explore the internal surfaces of the statue and acquire very important data for the technological study of the work. Particular attention was paid to cleaning the surfaces; once the materials accumulated over time were removed, partly residues of past interventions, it was possible to rediscover the beauty of the face, the refinement of the modeling and the high peculiarity of the wings. New technological solutions have been studied for the internal support that replaced the one inserted in the nineteenth century to hold the arms and wings of the statue, as it was no longer suitable for guaranteeing the safe conservation of the work. Since October 2020, the Winged Victory has been exhibited in the renovated Capitoline temple in Brescia, where it was discovered.

Salinity is a significant threat that causes considerable yield losses in date palm. The root endophytic fungus Piriformospora indica has proven effective in providing salt stress tolerance to host plants. However, the underlying molecular mechanism facilitating the date palm’s response to P. indica inoculation, and its involvement in the salt stress tolerance, remains unknown. In this study, the colonization of P. indica on date palm seedlings exposed to saline conditions was observed through confocal microscopy, and its impact on gene expressions was evaluated using the transcriptomic analysis. Our findings show that P. indica colonization reinforced the cortical cells, prevented them from plasmolysis and cell death under salinity. The RNAseq analysis produced clean reads ranging from 62,040,451 to 3,652,095 across the treatment groups, successfully assembling into 30,600 annotated genes. Out of them, the number of differentially expressed genes (DEGs) varied across the treatments: i.e., 2523, 2031, and 1936 DEGs were upregulated, while 2323, 959, and 3546 were downregulated in Salt, Fungi, and Fungi+Salt groups, respectively. Furthermore, principal component analysis based on transcriptome profiles revealed discrete clustering of samples from different treatment groups. KEGG and GO pathways enrichment analysis highlighted variation in the number and types of enriched pathways among the treatments. Our study indicated variations in gene expression related to plant hormone biosynthesis and signal transduction (auxin, abscisic acid, gibberellin, and ethylene), ABC transporters, sodium/hydrogen exchanger, cation HKT transporter, transcription factors such as WRKY and MYBs, and the plant immune system (lipoxygenase and jasmonate) of the date palm seedlings. By characterizing the transcriptome of date palm roots under salt stress and with colonization of P. indica, the present findings provide valuable perspectives on the molecular mechanisms responsible for inducing salinity stress tolerance in plants.

Abstract Mitochondrial and lysosomal activities are crucial to maintain cellular homeostasis: optimal coordination is achieved at their membrane contact sites where distinct protein machineries regulate organelle network dynamics, ions and metabolites exchange. Here we describe a genetically encoded SPLICS reporter for short- and long- juxtapositions between mitochondria and lysosomes. We report the existence of narrow and wide lysosome-mitochondria contacts differently modulated by mitophagy, autophagy and genetic manipulation of tethering factors. The overexpression of α-synuclein (α-syn) reduces the apposition of mitochondria/lysosomes membranes and affects their privileged Ca2+ transfer, impinging on TFEB nuclear translocation. We observe enhanced TFEB nuclear translocation in α-syn-overexpressing cells. We propose that α-syn, by interfering with mitochondria/lysosomes tethering impacts on local Ca2+ regulated pathways, among which TFEB mediated signaling, and in turn mitochondrial and lysosomal function. Defects in mitochondria and lysosome represent a common hallmark of neurodegenerative diseases: targeting their communication could open therapeutic avenues.

The functional characterization of PR10 proteins has been extensively studied in many plant species. However, little is known about the role of TdPR10 in the response of durum wheat (Triticum durum Desf.) to stress. In this study, we identified members of the T. durum PR10 family, which are divided into three major subfamilies based on phylogenetic analyses. The analysis revealed that tandem duplication was the primary driver of the expansion of the T. durum PR10 gene family. Additionally, gene structure and motif analyses showed that PR10 family genes were relatively conserved during evolution. We also identified several cis-regulatory elements in the TdPR10 promoter regions related not only to abiotic and biotic stress but also to phytohormonal responses. In response to abiotic stresses and phytohormones, several TdPR10 genes were highly expressed in the leaves and roots of durum wheat. Moreover, TdPR10.1 family members improve RNase activity, increase LDH protective activity under abiotic stress conditions, and ensure resistance to fungi in vitro. Collectively, these findings provide a basis for further functional studies of TdPR10 genes, which could be leveraged to enhance stress tolerance in durum wheat.

Increased soil salinization, tightly related to global warming and drought and exacerbated by intensified irrigation supply, implies highly detrimental effects on staple food crops such as wheat. The situation is particularly alarming for durum wheat (DW), better adapted to arid/semi-arid environments yet more sensitive to salt stress than bread wheat (BW). To enhance DW salinity tolerance, we resorted to chromosomally engineered materials with introgressions from allied halophytic Thinopyrum species. “Primary” recombinant lines (RLs), having portions of their 7AL arms distally replaced by 7el1L Th. ponticum segments, and “secondary” RLs, harboring Th. elongatum 7EL insertions “nested” into 7el1L segments, in addition to near-isogenic lines lacking any alien segment (CLs), cv. Om Rabia (OR) as salt tolerant control, and BW introgression lines with either most of 7el1 or the complete 7E chromosome substitution as additional CLs, were subjected to moderate (100 mM) and intense (200 mM) salt (NaCl) stress at early growth stages. The applied stress altered cell cycle progression, determining a general increase of cells in G1 and a reduction in S phase. Assessment of morpho-physiological and biochemical traits overall showed that the presence of Thinopyrum spp. segments was associated with considerably increased salinity tolerance versus its absence. For relative water content, Na+ accumulation and K+ retention in roots and leaves, oxidative stress indicators (malondialdehyde and hydrogen peroxide) and antioxidant enzyme activities, the observed differences between stressed and unstressed RLs versus CLs was of similar magnitude in “primary” and “secondary” types, suggesting that tolerance factors might reside in defined 7el1L shared portion(s). Nonetheless, the incremental contribution of 7EL segments emerged in various instances, greatly mitigating the effects of salt stress on root and leaf growth and on the quantity of photosynthetic pigments, boosting accumulation of compatible solutes and minimizing the decrease of a powerful antioxidant like ascorbate. The seemingly synergistic effect of 7el1L + 7EL segments/genes made “secondary” RLs able to often exceed cv. OR and equal or better perform than BW lines. Thus, transfer of a suite of genes from halophytic germplasm by use of fine chromosome engineering strategies may well be the way forward to enhance salinity tolerance of glycophytes, even the sensitive DW.

Abstract This study aims at examining the fertility impact of early childhood education and care (ECEC) services for children under three in Italy. ECEC is a social investment-oriented family policy that might have more beneficial effects on fertility than passive support in terms of transfers. We first present a systematic review of studies regarding the impact of ECEC on fertility in high-income countries and then provide an empirical analysis for Italy, a country with lowest-low fertility rates and a welfare system that has traditionally provided limited support to families, especially through ECEC. We combine micro-level data from the Labour Force Survey for Italy from years 2003–2020 with information on regional indicators of public childcare and private childcare. The study employs within-region variation in ECEC over time to assess its effects on the transition to parenthood and parity progression for different groups of women and men. The present contribution indicates that both public and private childcare services have limited but positive short-term effects on fertility behaviour in Italy, contingent on specific socio-demographic groups. We discuss the possible reasons for the constrained effect of childcare on fertility and emphasise the necessity for more substantial and concerted interventions in Italy’s family policies if the aim is to invert demographic trends of lowest fertility and population-ageing.

Recently, predicting the native structures of proteins has become possible using computational molecular physics (CMP)─physics-based force fields sampled with proper statistics─but only for small proteins. Algorithms with better scaling are needed. We describe ML x MELD x MD, a molecular dynamics (MD) method that inputs residue contacts derived from machine learning (ML) servers into MELD, a Bayesian accelerator that preserves detailed-balance statistics. Contacts are derived from trRosetta-predicted distance histograms (distograms) and are integrated into MELD's atomistic MD as spatial restraints through parametrized potential functions. In the CASP14 blind prediction event, ML x MELD x MD predicted 13 native structures to better than 4.5 Å error, including for 10 proteins in the range of 115-250 amino acids long. Also, the scaling of simulation time vs protein length is much better than unguided MD: tsim ∼ e0.023N for ML x MELD x MD vs tsim ∼ e0.168N for MD alone. This shows how machine learning information can be leveraged to advance physics-based modeling of proteins.

Wheat is the most consumed crop worldwide. Zeolite application combined with good tillage practices are good combinations that provide better soil conditions for wheat crops. Zeolite also provides a good layer for carbon to be absorbed into the soil and can retain carbon for hundreds of years. The current study aimed to investigate the effect of tillage practices and zeolite treatments on soil carbon retention and wheat crop productivity. Arranging the treatments implemented according to a factorial randomized block design which includes three replications. Tillage treatments include three levels vis: T1= 6 tillage practices with the help of cultivator (farmer practice/control), T2 (minimum tillage), and T3 (2 cultivation with cultivator + Mold-board plough). The zeolite applications consist of four levels: Z1 = 0, Z2 = 5, Z3 = 10 and Z4 = 15 t ha−1. The effect of the interaction between zeolite treatments and tillage practices on various factors related to soil and crops such as emission of carbon dioxide (CO2), dissolved organic carbon, soil organic carbon, and the productivity and components of wheat productivity. Zeolite applied at 10 t ha−1 in combination with minimum tillage gave significant differences in terms of CO2 emission, dissolved organic carbon, and on soil organic carbon. The experimental results showed that minimum CO2 emission (25.43 and 31.12 (kg CO2-C ha−1 h−1), dissolved organic carbon (4.80 and 4.90 g C kg−1), soil organic carbon (7.88 and 7.97 g C kg−1), plant height (92.14 and 92.97 cm), spike length (11.88 ad 12.11 cm), number of spikelets (20.11 and 20.98), number of tillers (278.65 and 283.93) per unit area, 1000 grain weight (50.74 and 51.54 g), biological yield (8134.87 and 8187.38 kg ha−1) and grain yield (2984.28 and 3028.96 kg ha−1) and harvest index (36.69 and 37.04%) of wheat was observed in zeolite applied at 10 t ha−1 with minimum tillage practice (T2 × Z3) compared to control and other treatments for both the years, respectively. It is therefore concluded that minimum tillage should be practiced in wheat crops with the application of zeolite at 10 t ha−1 to obtain better yield and soil carbon retention under rain-fed conditions.

Abstract In date palm, the LEA2 genes are of abundance with sixty-two members that are nearly all ubiquitous. However, their functions and interactions with potential target molecules are largely unexplored. In this study, five date palm LEA2 genes, PdLEA2.2, PdLEA2.3, PdLEA2.4, PdLEA2.6, and PdLEA2.7 were cloned, sequenced, and three of them, PdLEA2.2, PdLEA2.3, and PdLEA2.4 were functionally characterized for their effects on the thermostability of two distinct enzymes, lactate dehydrogenase (LDH) and β-glucosidase (bglG) in vitro. Overall, PdLEA2.3 and PdLEA2.4 were moderately hydrophilic, PdLEA2.7 was slightly hydrophobic, and PdLEA2.2 and PdLEA2.6 were neither. Sequence and structure prediction indicated the presence of a stretch of hydrophobic residues near the N-terminus that could potentially form a transmembrane helix in PdLEA2.2, PdLEA2.4, PdLEA2.6 and PdLEA2.7. In addition to the transmembrane helix, secondary and tertiary structures prediction showed the presence of a disordered region followed by a stacked β-sheet region in all the PdLEA2 proteins. Moreover, three purified recombinant PdLEA2 proteins were produced in vitro, and their presence in the LDH enzymatic reaction enhanced the activity and reduced the aggregate formation of LDH under the heat stress. In the bglG enzymatic assays, PdLEA2 proteins further displayed their capacity to preserve and stabilize the bglG enzymatic activity.