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Abstract In modern human societies, social isolation acts as a negative factor for health and life quality. On the other hand, social interaction also has profound effects on animal and human, impacting aggressiveness, feeding and sleep, among many other behaviors. Here, we observe that in the fly Drosophila melanogaster these behavioral changes long-last even after social interaction has ceased, suggesting that the socialization experience triggers behavioral plasticity. These modified behaviors maintain similar levels for 24 h and persist up to 72 h, although showing a progressive decay. We also find that impairing long-term memory mechanisms either genetically or by anesthesia abolishes the expected behavioral changes in response to social interaction. Furthermore, we show that socialization increases CREB-dependent neuronal activity and synaptic plasticity in the mushroom body, the main insect memory center analogous to mammalian hippocampus. We propose that social interaction triggers socialization awareness, understood as long-lasting changes in behavior caused by experience with mechanistic similarities to long-term memory formation.

BackgroundPrior epidemiologic studies on the association between diabetes and gastric cancer risk provided inconclusive findings, while traditional, aggregate data meta-analyses were characterized by high between-study heterogeneity.ObjectiveTo investigate the association between type 2 diabetes and gastric cancer using data from the 'Stomach Cancer Pooling (StoP) Project', an international consortium of more than 30 case-control and nested case-control studies, which is large and provides harmonized definition of participants' characteristics across individual studies. The data have the potential to minimize between-study heterogeneity and provide greater statistical power for subgroup analysis.MethodsWe included 5592 gastric cancer cases and 12 477 controls from 14 studies from Europe, Asia, North America, and South America in a two-stage individual-participant data meta-analysis. Random-effect models were used to estimate summary odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) by pooling study-specific ORs.ResultsWe did not find an overall association between diabetes and gastric cancer (pooled OR = 1.01, 95% CI, 0.94-1.07). However, the risk of cardia gastric cancer was significantly higher among individuals with type 2 diabetes (OR = 1.16, 95% CI, 1.02-1.33). There was no association between diabetes and gastric cancer risk in strata of Helicobacter pylori infection serostatus, age, sex, BMI, smoking status, alcohol consumption, fruit/vegetable intake, gastric cancer histologic type, and source of controls.ConclusionThis study provides additional evidence that diabetes is unrelated to gastric cancer overall but may be associated with excess cardia gastric cancer risk.

Abstract This study estimated biomass and carbon from components, future carbon values and to obtain economic productive value of carbon fixation of a Seasonal Semideciduous Forest. Biomass and carbon were estimated using adjusted equations and selected using regression statistics. The prognosis of the diametric distribution was performed using the movement ratio method. In the economic evaluation, it was estimated productive value of the stand, referring to the current and future carbon fixation capacity. The coefficients of determination (adjusted R²) of the equations ranged from 0.11 to 0.90 and the standard error of the estimate (Syx) ranged from 41.53% to 141.89% for the biomass of the components, and from 0.03 to 0.87 for adjusted R² and from 46.20% to 143.64% for the error, for stored carbon in the components. The total biomass of the tree component estimated was 56.25 t ha-1 and 25.88 t ha-1 of total carbon. Using the future distributions by the method of the ratio of movements, total stored carbon (aerial + roots) estimated was 14.44 t. ha-1 over the 20-year period. The productive value for the fragment reached R$ 299.95 per ha. year-1.

The DFNA58 locus contains a genomic duplication involving three protein-coding genes (CNRIP1, PLEK, and PPP3R1′s exon 1) and other uncharacterized lncRNA genes (LOC101927723, LOC107985892 and LOC102724389). To clarify the role of these genes in hearing and precisely determine their role in hearing loss, four iPSC lines were generated from two carriers and two noncarriers of the duplication.

Abstract Background Acid sphingomyelinase deficiency (ASMD) is a lysosomal disorder caused by deficiency of acid sphingomyelinase (ASM) leading to the accumulation of sphingomyelin (SM) in a variety of cell types. Lysosphingomyelin (LysoSM) is the de-acetylated form of SM and it has been shown as a biomarker for ASMD in tissues, plasma, and dried blood spots (DBS) and lysosphingomyelin-509 (LysoSM509) is the carboxylated analogue of LysoSM. High levels of Lysosphingomyelin 509 (LysoSM509) have also been shown in ASMD patients. In this study, we report the utility of the quantification of LysoSM and LysoSM509 in DBS of patients from Latin America with ASMD by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results DBS samples from 14 ASMD patients were compared with 15 controls, and 44 general newborns. All patients had their diagnosis confirmed by the quantification of ASM and the measurement of the activity of chitotriosidase. All patients had significantly higher levels of lysoSM and lysoSM509 compared to controls and general newborns. Conclusions The quantification of lysosphingolipids in DBS is a valuable tool for the diagnosis of ASMD patients and lysoSM can be useful in the differential diagnosis with NPC. This method is also valuable in the ASMD newborn screening process.

Visceral adiposity is a risk factor for severe COVID-19, and infection of adipose tissue by SARS-CoV-2 has been reported. Here the authors confirm that human adipose tissue is a possible site for SARS-CoV-2 infection, but the degree of adipose tissue infection and the way adipocytes respond to the virus depend on the adipose tissue depot and the viral strain.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the agent of a major global outbreak of respiratory tract disease known as Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 infects mainly lungs and may cause several immune-related complications, such as lymphocytopenia and cytokine storm, which are associated with the severity of the disease and predict mortality. The mechanism by which SARS-CoV-2 infection may result in immune system dysfunction is still not fully understood. Here, we show that SARS-CoV-2 infects human CD4+ T helper cells, but not CD8+ T cells, and is present in blood and bronchoalveolar lavage T helper cells of severe COVID-19 patients. We demonstrated that SARS-CoV-2 spike glycoprotein (S) directly binds to the CD4 molecule, which in turn mediates the entry of SARS- CoV-2 in T helper cells. This leads to impaired CD4 T cell function and may cause cell death. SARS-CoV-2-infected T helper cells express higher levels of IL-10, which is associated with viral persistence and disease severity. Thus, CD4-mediated SARS-CoV-2 infection of T helper cells may contribute to a poor immune response in COVID-19 patients.

A clear understanding of landslide mechanisms and stability analyses is of great significance for landslide monitoring, prediction, and control. A large-scale end wall landslide occurred and its area reached 47,752 m2 on August 7–20, 2020, in the Manglai open-pit coal mine, China. In this paper, the engineering geological survey, mechanical test, large-deformation finite element numerical method, limit equilibrium method and analytical formula are used to analyze how the groundwater level rise caused this end wall failure and landslide. The engineering geological conditions, hydrogeological conditions, landslide activity signs and physical and mechanical parameter calibration of the sliding mass are investigated in detail and tested. Three-dimensional and two-dimensional numerical models of slopes are established, and an analytical formula calculation method to calculate the factor of safety (FoS) is proposed when sliding cracks are located on the top and toe of a slope. The results indicate that the fault fracture zone, soft strata, continuous heavy rainfall, and groundwater were the main contributors to this landslide. The three-dimensional numerical calculation results are consistent with the deformation and failure process of the slope observed in the field, which shows a retrogressive progressive failure mode. The calculation results of SLOPE/W and the analytical formula are consistent; i.e., when the groundwater level rises to +950, the stability of the end wall reaches the critical stability state. With the passage of time, the creep of the sliding surface accelerates until the entire end wall landslide.

It is important to understand whether endothelial cells are epigenetically affected by titanium-enriched media when angiogenesis is required during bone development and it is expected to be recapitulated during osseointegration of biomaterials. To better address this issue, titanium-enriched medium was obtained from incubation of titanium discs for up to 24 h as recommended by ISO 10993-5:2016, and further used to expose human umbilical vein endothelial cells (HUVECs) for up to 72 h, when the samples were properly harvested to allow molecular analysis and epigenetics. In general, our data show an important repertoire of epigenetic players in endothelial cells responding to titanium, reinforcing protein related to the metabolism of acetyl and methyl groups, as follows: Histone deacetylases (HDACs) and NAD-dependent deacetylase sirtuin-1 (Sirt1), DNA methyltransferases (DNMTs) and ten-eleven translocation (TET) methylcytosine dioxygenases, which in conjunction culminate in driving chromatin condensation and the methylation profile of DNA strands, respectively. Taking our data into consideration, HDAC6 emerges as important player of this environment-induced epigenetic mechanism in endothelial cells, while Sirt1 is required in response to stimulation of reactive oxygen species (ROS) production, as its modulation is relevant to vasculature surrounding implanted devices. Collectively, all these findings support the hypothesis that titanium keeps the surrounding microenvironment dynamically active and so affects the performance of endothelial cells by modulating epigenetics. Specifically, this study shows the relevance of HDAC6 as a player in this process, possibly correlated with the cytoskeleton rearrangement of those cells. Furthermore, as those enzymes are druggable, it opens new perspectives to consider the use of small molecules to modulate their activities as a biotechnological tool in order to improve angiogenesis and accelerate bone growth with benefits of a fast recovery time for patients.

Abstract Background Liver organoid technology holds great promises to be used in large-scale population-based drug screening and in future regenerative medicine strategies. Recently, some studies reported robust protocols for generating isogenic liver organoids using liver parenchymal and non-parenchymal cells derived from induced pluripotent stem cells (iPS) or using isogenic adult primary non-parenchymal cells. However, the use of whole iPS-derived cells could represent great challenges for a translational perspective. Methods Here, we evaluated the influence of isogenic versus heterogenic non-parenchymal cells, using iPS-derived or adult primary cell lines, in the liver organoid development. We tested four groups comprised of all different combinations of non-parenchymal cells for the liver functionality in vitro. Gene expression and protein secretion of important hepatic function markers were evaluated. Additionally, liver development-associated signaling pathways were tested. Finally, organoid label-free proteomic analysis and non-parenchymal cell secretome were performed in all groups at day 12. Results We show that liver organoids generated using primary mesenchymal stromal cells and iPS-derived endothelial cells expressed and produced significantly more albumin and showed increased expression of CYP1A1, CYP1A2, and TDO2 while presented reduced TGF-β and Wnt signaling activity. Proteomics analysis revealed that major shifts in protein expression induced by this specific combination of non-parenchymal cells are related to integrin profile and TGF-β/Wnt signaling activity. Conclusion Aiming the translation of this technology bench-to-bedside, this work highlights the role of important developmental pathways that are modulated by non-parenchymal cells enhancing the liver organoid maturation.

The waste dump is a giant artificial loose pile body composed of fine, medium, and coarse particle sizes. Rising incidents of landslides caused by overburden pressure and effective pressure are of increasing concern in the open-pit waste dump and, if not well-controlled, are a dangerous threat to the workers, the environment, and the equipment. The purpose of this research is to investigate the connection between effective pressure, porosity, void ratio, and coefficient of permeability and to find their influence in the open-pit waste dump. This study analyzed the mechanical and physical changes of seven different soil samples using consolidation and permeability under consolidation laboratory test. The test samples were subject to a pressure ranging from 100 to 1600 kPa. The effective pressure was found to play a major role in influencing void ratio, porosity, and coefficient of permeability, and waste dump height management and control are of great importance. This study answers the question regarding the correlation between effective pressure, void ratio, porosity, and coefficient of permeability in the open-pit waste dump. Further studies are needed to establish profound relationships and develop preventative measures to keep the waste dump slope stable and safe.

The non-uniformly distributed calcareous concretion among the oil shale in the Junggar basin of China has led to the difficulty in achieving the slope stability. This paper presents the numerical simulation of the behavior of oil shale with calcareous concretion via the Particle Flow Code (PFC2D) program based on the trial experimental test results. The critical parameters investigated in this research covered the size, distribution, strength, and number of the calcareous concretion. The following conclusions can be drawn based on the discussions and analysis: (1) the hard concretion always results in the high compressive strength of the specimen compared with that without concretion; (2) when the radius of the concretion size raised from 2.5 mm to 20 mm, the peak strength of tested specimens is approximately 50 MPa, whereas, the specimen with large concretion is much more ductile under compression; (3) the compressive behavior of tested specimens is similar even when the position of the concretion is variable; and (4) different from the specimens with only one concretion, these specimens contained two concretions featured with the double “X” failure mode. Meanwhile, the peak strength of the specimens with two hard concretions is about 2.5 times that of its counterparts with two soft concretions. The numerical simulation results are meaningful in guiding the design and analysis of the oil shale slope with the concretion.

Repeats in coding and non-coding regions have increasingly been associated with many human genetic disorders, such as Richieri-Costa-Pereira syndrome (RCPS). RCPS, mostly characterized by midline cleft mandible, Robin sequence and limb defects, is an autosomal-recessive acrofacial dysostosis mainly reported in Brazilian patients. This disorder is caused by decreased levels of EIF4A3, mostly due to an increased number of repeats at the EIF4A3 5′UTR. EIF4A3 5′UTR alleles are CG-rich and vary in size and organization of three types of motifs. An exclusive allelic pattern was identified among affected individuals, in which the CGCA-motif is the most prevalent, herein referred as “disease-associated CGCA-20nt motif.” The origin of the pathogenic alleles containing the disease-associated motif, as well as the functional effects of the 5′UTR motifs on EIF4A3 expression, to date, are entirely unknown. Here, we characterized 43 different EIF4A3 5′UTR alleles in a cohort of 380 unaffected individuals. We identified eight heterozygous unaffected individuals harboring the disease-associated CGCA-20nt motif and our haplotype analyses indicate that there are more than one haplotype associated with RCPS. The combined analysis of number, motif organization and haplotypic diversity, as well as the observation of two apparently distinct haplotypes associated with the disease-associated CGCA-20nt motif, suggest that the RCPS alleles might have arisen from independent unequal crossing-over events between ancient alleles at least twice. Moreover, we have shown that the number and sequence of motifs in the 5′UTR region is associated with EIF4A3 repression, which is not mediated by CpG methylation. In conclusion, this study has shown that the large number of repeats in EIF4A3 does not represent a dynamic mutation and RCPS can arise in any population harboring alleles with the CGCA-20nt motif. We also provided further evidence that EIF4A3 5′UTR is a regulatory region and the size and sequence type of the repeats at 5′UTR may contribute to clinical variability in RCPS.

Glycoside Hydrolases (GHs) are enzymes able to recognize and cleave glycosidic bonds. Insect GHs play decisive roles in digestion, in plant-herbivore, and host-pathogen interactions. GH activity is normally measured by the detection of a release from the substrate of products as sugars units, colored, or fluorescent groups. In most cases, the conditions for product release and detection differ, resulting in discontinuous assays. The current protocols result in using large amounts of reaction mixtures for the obtainment of time points in each experimental replica. These procedures restrain the analysis of biological materials with limited amounts of protein and, in the case of studies regarding small insects, implies in the pooling of samples from several individuals. In this respect, most studies do not assess the variability of GH activities across the population of individuals from the same species. The aim of this work is to approach this technical problem and have a deeper understanding of the variation of GH activities in insect populations, using as models the disease vectors Rhodnius prolixus (Hemiptera: Triatominae) and Lutzomyia longipalpis (Diptera: Phlebotominae). Here we standardized continuous assays using 4-methylumbelliferyl derived substrates for the detection of α-Glucosidase, β-Glucosidase, α-Mannosidase, N-acetyl-hexosaminidase, β-Galactosidase, and α-Fucosidase in the midgut of R. prolixus and L. longipalpis with results similar to the traditional discontinuous protocol. The continuous assays allowed us to measure GH activities using minimal sample amounts with a higher number of measurements, resulting in data that are more reliable and less time and reagent consumption. The continuous assay also allows the high-throughput screening of GH activities in small insect samples, which would be not applicable to the previous discontinuous protocol. We applied continuous GH measurements to 90 individual samples of R. prolixus anterior midgut homogenates using a high-throughput protocol. α-Glucosidase and α-Mannosidase activities showed the normal distribution in the population. β-Glucosidase, β-Galactosidase, N-acetyl-hexosaminidase, and α-Fucosidase activities showed non-normal distributions. These results indicate that GHs fluorescent-based high-throughput assays apply to insect samples and that the frequency distribution of digestive activities should be considered in data analysis, especially if a small number of samples is used.