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The nucleolus is a nuclear body where different important molecular processes occurs. Beyond ribosomal biogenesis, other relevant functions were recently assigned to this nuclear region, which are related to cell proliferation control and apoptosis, involvement in telomere formation, transfer RNA modifications and stress sensing. Morphologically it is organized in three main areas: roundish electron-light regions, known as Fibrillar Centers (FCs), surrounded by the Dense Fibrillar Component (DFC). These fibrillary structures lie inside the Granular Component (GC), which constitutes most of the nucleolus. Moreover patches of heterochromatin delimitate the nucleolar periphery, interspaced by euchromatin, with thin strands of condensed chromatin enter the nucleolar body. Some aspects of nucleolar morphology have been correlated to their corresponding molecular activity. It is established that rDNA is present within the FC, DFC, in the perinucleolar heterochromatin and in its intranucleolar strands, whereas ribosomal RNA was localized to DFC and GC. rRNA transcription occurs in the FC/DFC complex, while outside the nucleolus reside transcriptionally inactive rDNA repeats. However we still have little knowledge about the condensed regions of perinucleolar heterochromatin. In order to characterize the molecular activity of this area, we decided to investigate its epigenetics status. We hypothesized that, being a condensed region, it would show the classical markers of repression find in the other nuclear regions characterized by compact chromatin. Indeed we analysed at ultrastructural level the distribution of the histone markers H3K27me3 and H3K9me3, which are known to be involved in chromatin condensation and gene silencing. This study was carried out by immunocytochemistry of these histone marker distributions at electron microscopy. Moreover quantifications and statistics of the marker distributions using bioinformatics tools were carried out. We were able to highlight that not only in all compact regions of the nuclear and nucleolar heterochromatin these two repressive histone markers were present, but also that they were specifically confined to the heterochromatin. From our analysis no significant difference in their density or distributions were found between the nucleolar associated and nuclear heterochromatin. Considering these results, we hypothesize that the general mechanisms of chromatin condensation which involve H3K27me3 and H3K9me3 could be similar in different nuclear domains.

Methylation and demethylation are two epigenetic processes of a big relevance for different biological pathways. The two events happen on the carbon in position five of the cytosine belonging to the so called CpG island. The methylation implies the addition of a methyl group on the cytosine, forming the 5-methylcytosine (5mC) thanks to enzymes called DNMT (Dna-Methyltransferase). After, when required, the methyl group is oxidized or demethylated by a family of enzyme called TET, forming the 5-hydroxymethylcytosine (5hmC). The role of the 5mC is generally correlated with gene expression repression, while the 5hmC function must be clarified. In this context, in order to elucidate the hypothetic role of these markers we decide to investigate at ultrastructural level, by looking at the distribution of two epigenetic modifications putting our attention on different areas of the cell nucleus. Our study where carried out by using transmission electron microscope, light microscope and molecular biology techniques. We observed that in condensed regions of the nucleus the DNA is always highly methylated rather than hydroxymethylated, but in the so called perichromatin region the pattern changes. Indeed, in this region it was possible to notice an abundancy of demethylation underlined both by the presence of the 5hmC and of the enzymes involved in the processes: TET2. This result could allow to hypothesize a sort of activating role for the oxidized modification respect to its reduced form and underline how the perichromatin region is a dynamic region where DNA status changes.

Objectives To describe clinical characteristics, laboratory tests, radiological data and outcome of pediatric cases with SARS-CoV-2 infection complicated by neurological involvement. Study design A computerized search was conducted using PubMed. An article was considered eligible if it reported data on pediatric patient(s) with neurological involvement related to SARS-CoV-2 infection. We also described a case of an acute disseminated encephalomyelitis (ADEM) in a 5-year-old girl with SARS-CoV-2 infection: this case was also included in the systematic review. Results Forty-four articles reporting 59 cases of neurological manifestations in pediatric patients were included in our review. Most (32/59) cases occurred in the course of a multisystem inflammatory syndrome in children (MIS-C). Neurological disorders secondary to cerebrovascular involvement were reported in 10 cases: 4 children with an ischemic stroke, 3 with intracerebral hemorrhage, 1 with a cerebral sinus venous thrombosis, 1 with a subarachnoid hemorrhage, 1 with multiple diffuse microhemorrhages. Reversible splenial lesions were recognized in 9 cases, benign intracranial hypertension in 4 patients, meningoencephalitis in 4 cases, autoimmune encephalitis in 1 girl, cranial nerves impairment in 2 patients and transverse myelitis in 1 case. Five cases had Guillain-Barré syndrome (GBS) and two, including ours, had ADEM. Radiological investigations were performed in almost all cases (45/60): the most recurrent radiological finding was a signal change in the splenium of the corpus callosum. The presence of SARS-CoV-2 viral nucleic acid in the cerebrospinal fluid was proved only in 2 cases. The outcome was favorable in almost all, except in 5 cases. Conclusions Our research highlights the large range of neurological manifestations and their presumed pathogenic pathways associated with SARS-CoV-2 infection in children. Nervous system involvement could be isolated, developing during COVID-19 or after its recovery, or arise in the context of a MIS-C. The most reported neurological manifestations are cerebrovascular accidents, reversible splenial lesions, GBS, benign intracranial hypertension, meningoencephalitis; ADEM is also a possible complication, as we observed in our patient. Further studies are required to investigate all the neurological complications of SARS-CoV-2 infection and their underlying pathogenic mechanism.

Open, accessible, reusable, and reproducible hydrologic research can have a significant positive impact on the scientific community and broader society. While more individuals and organizations within the hydrology community are embracing open science practices, technical (e.g., limited coding experience), resource (e.g., open access fees), and social (e.g., fear of weaknesses being exposed or ideas being scooped) challenges remain. Furthermore, there are a growing number of constantly evolving open science tools, resources, and initiatives that can be overwhelming. These challenges and the ever-evolving nature of the open science landscape may seem insurmountable for hydrologists interested in pursuing open science. Therefore, we propose the general “Open Hydrology Principles” to guide individual and community progress toward open science for research and education and the “Open Hydrology Practical Guide” to improve the accessibility of currently available tools and approaches. We aim to inform and empower hydrologists as they transition to open, accessible, reusable, and reproducible research. We discuss the benefits as well as common open science challenges and how hydrologists can overcome them. The Open Hydrology Principles and Open Hydrology Practical Guide reflect our knowledge of the current state of open hydrology; we recognize that recommendations and suggestions will evolve and expand with emerging open science infrastructures, workflows, and research experiences. Therefore, we encourage hydrologists all over the globe to join in and help advance open science by contributing to the living version of this document and by sharing open hydrology resources in the community-supported repository (https://open-hydrology.github.io, last access: 1 February 2022).

Photosynthesis and translation are targets of metabolic control and development in plants, yet how stress signals coordinately regulate these opposing energy-producing and consuming processes remains enigmatic. Here, we unravel a growth control circuit that ties photosynthesis to translational control in response to biotic and abiotic signals. Our findings reveal that the L10-INTERACTING MYB DOMAIN-CONTAINING PROTEIN (LIMYB), a key player of the NUCLEAR SHUTTLE PROTEIN-INTERACTING KINASE 1 (NIK1)/ RIBOSOMAL PROTEIN L10 (RPL10) antiviral signaling pathway, not only downregulates translation genes, but also represses photosynthesis-related genes and photosynthesis itself. LIMYB repressor activity, regulated by phosphorylation, is crucial for the decline in photosynthesis under stress. NIK1 activation by PAMPs or the phosphomimetic NIK1-T474D represses photosynthesis-related genes and photosynthesis in control but not in limyb lines. Furthermore, heat and osmotic stress also activate the NIK1/RPL10/LIMYB signaling circuit in wild type. These stresses induce NIK1 phosphorylation, but not marker gene repression, in limyb , indicating that LIMYB connects NIK1 activation to stress-mediated downregulation of translation- and photosynthesis-related genes. This coordinated repression via the NIK1/RPL10/LIMYB module may help plants adapt to changing environments. The receptor-like kinase NIK1 is phosphorylated in response to multiple biotic and abiotic signals, activating the NIK1/RPL10/LIMYB signaling circuit, which coordinately regulates translation and photosynthesis in response to environmental changes.

Quantification of seasonal dynamics of soil C and N pools is crucial to understand the land management practices for enhancing agricultural sustainability. In a cover crop (CC) experiment established in 2007 and repeated at an adjacent site in 2008, we evaluated the medium-term impact of CC (no cover crop control (no-CC), oat (Avena sativa L.), oilseed radish (OSR, Raphanus sativus L. var. oleoferus Metzg. Stokes), winter cereal rye (rye, Secale cereale L.), and a mixture of OSR+Rye) and crop residue management (residue removed (-R) and residue retained (+R)) on soil C and N dynamics and sequestration. Labile and stable fractions of C and N were determined at seven different time points from 0-15 cm depth during tomato (Solanum lycopersicum L.) growing season in 2015 and 2016 (referred to as site-years). As expected, over the tomato growing season in both site-years, organic C (OC) and total N did not change while the labile C and N fractions changed with greater concentrations observed at 2 weeks after tillage (WAT) and greater treatment differences observed for seven out of eleven soil attributes at tomato harvest. Therefore, 2WAT (early June) and tomato harvest (early September) are reasonably optimum sampling times for soil C and N attributes. Seasonal variation of labile fractions suggested the potential impact of substrate availability from crop residues on soil C and N cycling. Medium-term CC usage enhanced the surface soil C and N storage. Overall, this study highlights the positive and synergistic influences of CCs and maintaining crop residues in increasing both labile and stable fractions of C and N and enhancing soil quality in a temperate humid climate.

Transcatheter aortic valve implantation (TAVI) has emerged as an effective and safe treatment for patients with symptomatic aortic stenosis. The indication to TAVI should be agreed upon by a Heart Team, and the procedure should be performed in centers with on-site cardiac surgery. However, TAVI complications requiring emergent cardiac surgery (ECS) have become very rare. Concurrently, access disparities and prolonged waiting times are pressing issues due to increasing clinical demand of TAVI. Many solutions have been proposed and one of them is the possibility of performing TAVI in centers without on-site cardiac surgery. The Transcatheter Aortic-Valve Implantation with or without on-site Cardiac Surgery (TRACS) trial is a prospective, randomized, multicenter, open-label study with blinded adjudicated evaluation of outcomes. Patients with symptomatic severe aortic stenosis and deemed inoperable, at high surgical risk, or presenting with at least 1 clinical factor compromising the benefit/risk ratio for ECS, will be randomized to undergo TAVI either in centers with or without on-site cardiac surgery. The primary endpoint will be the composite occurrence of all-cause death, stroke, and hospital readmission for cardiovascular causes at one year. The safety endpoint will include death attributable to periprocedural complications actionable by ECS. The study aims to enroll 566 patients. The TRACS trial aims to address critical gaps in knowledge regarding the safety and efficacy of TAVI procedures performed in centers without on-site cardiac surgery, potentially improving access and outcomes for high-risk patients. ClinicalTrials.gov NCT05751577 [Display omitted]

BackgroundRheumatoid arthritis (RA) prevalence is believed to be around 1% worldwide, although it varies considerably among different populations.[1] Several environmental factors such as smoking, certain infections, and diet contribute to the risk of RA and differ between populations.[2] The pooled prevalence of RA was estimated to be 0.54% (95% CI 0.50–0.59) in Europe,[1] but no studies have recently evaluated the epidemiology of RA in Italy.ObjectivesWe aimed at estimating the incidence and prevalence of RA in northeastern Italy over the period 2012–2020.MethodsA retrospective population-based study was conducted in the Veneto Region (4.9 million people) using the Population Registry, an administrative health database where all residents are recorded. The population registry was linked with healthcare co-payments exemptions, hospital discharge records, and mortality records. Between 2012 and 2020, RA prevalence was defined by a healthcare copayment exemption for RA (national registry code 006) or any hospital diagnosis of RA (ICD-9-CM 714.x), whichever came first. Incident RA was defined from 2013 to 2020 to exclude prevalent cases. Standardized incidence and prevalence rates were reported by age and gender.ResultsDuring the study period, we identified 37,996 prevalent RA patients, with 12,875 incident cases. Across the study period, RA standardized prevalence increased from 0.50% (95% CI 0.50; 0.51) to 0.57% (95% CI 0.57; 0.58). RA point prevalence in 2020 according to gender and age is reported in Figure 1. RA incidence corresponded to 33.1 (32.5; 33.7) per 100,000 person-years, with the lowest incidence observed in the last two years of the study: 27.4 (25.9; 28.9) in 2020 and 32.2 (30.6; 33.8) in 2019 (Table 1). The peak for both prevalence and incidence was around the eighth decade of life. Incidence was 2-times higher in females: female-to-male incidence rate ratio (IRR) 2.3 (2.2; 2.4) (p<0.0001), with a peak among people aged 20-29 years, where female-to-male IRR was 3.1 (2.4; 3.9) and the lowest value among patients aged ≥70 years, where F:M IRR was 1.6 (1.4; 1.8).ConclusionThe prevalence of RA in Italy is 0.57%, in line with data from other European countries. Incidence was confirmed to be higher among females, especially in younger patients.References[1]Almutairi K et al. The global prevalence of rheumatoid arthritis: a meta-analysis based on a systematic review. Rheumatol Int 2021;41:863–877.[2]Tobon, GJ, et al. The environment, geo-epidemiology, and autoimmune disease: Rheumatoid arthritis. J Autoimmun 2010;35:10–14.Figure 1.The point prevalence of Rheumatoid Arthritis in The Veneto Region in 2020 by age and gender.Table 1.Incidence of Rheumatoid Arthritis in the Veneto Region between 2013 and 2020.YearNew diagnosis, numberPopulationCrude rate (95%IC) x 100,000Standardized IR (95%IC)x100,000*New diagnosis, numberStandardized IR (95%IC)x100,000*MaleFemaleMaleFemale20131.6154.901.41532.9 (31.3; 34.6)34.2 (32.5; 35.8)475114020.8 (18.9; 22.7)46.9 (44.1; 49.6)20141.7384.905.71235.4 (33.8; 37.1)36.4 (34.7; 38.1)508123021.9 (20.0; 23.9)50.2 (47.3; 53.0)20151.5754.902.69432.1 (30.5; 33.7)32.7 (31.1; 34.3)462111319.8 (18.0; 21.6)45.0 (42.4; 47.7)20161.6254.890.64833.2 (31.6; 34.8)33.5 (31.9; 35.2)487113820.7 (18.8; 22.5)45.8 (43.1; 48.5)20171.6514.883.37333.8 (32.2; 35.4)33.8 (32.2; 35.4)461119019.4 (17.6; 21.1)47.6 (44.9; 50.3)20181.7104.880.93635.0 (33.4; 36.7)34.8 (33.1; 36.4)504120620.9 (19.1; 22.7)48.0 (45.3; 50.7)20191.5964.884.59032.7 (31.1; 34.3)32.2 (30.6; 33.8)463113319.0 (17.3; 20.8)44.8 (42.2; 47.4)20201.3654.879.13328.0 (26.5; 29.5)27.4 (25.9; 28.9)40695916.5 (14.9; 18.1)37.8 (35.4; 40.2)TOT**12.87539.128.50132.9 (32.3; 33.5)33.1 (32.5; 33.7)3766910919.9 (19.2; 20.5)45.7 (44.8; 46.6)Acknowledgements:NIL.Disclosure of InterestsMargherita Zen Speakers bureau: Abbvie, Ely Lilly, GSK, Galapagos, AstraZeneca, Laura Salmaso: None declared, Claudio Barbiellini Amidei: None declared, Alessandro Giollo Speakers bureau: Galapagos, Abbvie, Ugo Fedeli: None declared, Stefania Bellio: None declared, Federico Arru: None declared, Ilenia Gennaio: None declared, Mario Saia: None declared, Andrea Doria Speakers bureau: GSK, AstraZeneca, UCB, Pfizer, Consultant of: GSK, AstraZeneca.

Whether or not in the last years mortality is still increased in RA patients compared to the general population is controversial. To assess mortality rates (MRs), standardized mortality ratios (SMRs), and causes of death in Rheumatoid Arthritis (RA) in a population-based study. We analyzed linked administrative health databases of the Veneto Region (Italy, 4,900,000 residents): the population registry, where all residents are recorded, was linked with healthcare co-payments exemptions, hospital discharge records, and mortality records. RA was defined by a healthcare copayment exemption for or any hospital diagnosis of RA. We analyzed all-cause mortality until December 31, 2020. MRs per 1,000 were stratified by year, sex, and age group. SMRs were derived, by comparing MRs of the general regional population. Causes of death were coded using the ICD-10 coding system and were available until 31/12/2020; they were grouped in: RA, infectious diseases, cardiovascular diseases (CVD), cancer, diabetes, or others. Between 2012 and 2020, 7,435 deaths among 37,996 RA prevalent cases occurred, corresponding to an average annual standardized MR of 32.2 (95% CI 31.5; 33.0) per 1,000 persons. The median (IQR) age at death was 83 years (77-88), lower in males (81, 75-86) compared to females (84, 78-89). Standardized MR was higher in males than in females (41.3, 95% 39.05-43.2 vs. 29.5, 95% CI 28.7-30.3); notably, this was true across all age groups (Table 1). Causes of death were CVD 2,735 (37.1%), cancer 1,519 (20.6%), infections 827 (11.2%), RA 352 (4.8%), diabetes 208 (2.8%), trauma, poisoning, or post-surgical/procedural complications 197 (2.7%), and others 1,532 (20.6%). Out of 12,875 incident RA patients, 1,288 died during the study period, corresponding to a mortality rate of 21.3 (95% CI 20.2-22.5). The distribution of causes of death among incident cases was comparable to that observed among prevalent cases. Overall SMR was 1.28 (95% CI 1.21-1.35) and was higher in younger patients (<45 years old: 2.15, 95% CI 0.93-4.24) (Figure 1). Eight-year survival was significantly affected by age at diagnosis: 98.8% (95% CI 98.1%-99.2%) in patients aged <50 years, 95.8% (94.5%-96.8%) in patients aged 50-59, 94.2% (92.2%-95.7%) in patients aged 60-64, 84.1% (81.7%-86.2%) in those aged 65-75, and 48.4% (45%-51.6%) in those aged >75 years. Standardized mortality ratio is slightly increased in RA patients compared to the general population, especially in younger patients. Despite that, eight-year survival in subjects <49 is good. CVD and cancer represent the main causes of death in RA, whereas therapy-related complications such as infections account for a low proportion of deceases. NIL. NIL. None Declared. [Display omitted] Table 1Deaths and mortality rates among 37,996 prevalent RA cases (2012 - 2021).YearPatients at Jan 1stDeaths Jan 1st - Dec 31stRate x1000 residents with RAStandardized mortality rates x1000 residents (95% CI)TOTMFTOTMFTOTMFTOTMF20122340258111759170519950630,134,228,834,3 (31,8; 36,9)46,8 (39,9; 53,8)30,7 (28,0; 33,4)20132403559831805272120152030,033,628,832,7 (30,3; 35,1)43,5 (37,2; 49,9)29,4 (26,8; 31,9)20142471561941852171319951428,832,127,830,8 (28,5; 33,1)39,0 (33,4; 44,6)27,9 (25,5; 30,3)20152555764361912181420960531,932,531,633,1 (30,8; 35,3)39,8 (34,2; 45,4)31,1 (28,7; 33,6)20162617366561951779721658130,532,529,830,9 (28,8; 33,1)37,6 (32,4; 42,7)28,6 (26,3; 30,9)20172692869242000488324863532,835,831,732,8 (30,6; 35,0)41,9 (36,5; 47,2)30,2 (27,8; 32,5)20182758270952048788726162632,236,830,631,5 (29,4; 33,6)41,9 (36,7; 47,1)28,6 (26,3; 30,8)20192823972962094388824264631,433,230,830,4 (28,4; 32,4)37,3 (32,5; 42,1)28,3 (26,1; 30,5)202028740744621294102730472335,740,834,033,7 (31,6; 35,8)45,0 (39,8; 50,1)30,5 (28,2; 32,7)2012-20202353715984117553074352079535631,634,730,532,2 (31,5; 33,0)41,3 (39,5; 43,2)29,5 (28,7; 30,3)

This study compared the behavior of the biomass in two fixed-film anaerobic reactors operated under equivalent organic loading rates but at different temperatures, i.e., 30 °C (RMM) and 55 °C (RMT). The reactors were fed with sugarcane vinasse and molasses (both fermented) in a simulation of sequential periods of season and off-season. The dynamics of biomass growth and retention, as well as the microbial composition, were assessed throughout 171 days of continuous operation, coupled with an additional 10-day test assessing the microbial activity in the bed region. Despite the different inoculum sources used (mesophilic granular vs. thermophilic flocculent sludge types), the biomass growth yield was identical (0.036–0.038 g VSS g−1COD) in both systems. The retention rates (higher in RMT) were regulated according to the initial amount of biomass provided in the inoculation, resulting in similar amounts of total retained biomass (46.8 vs. 43.3 g VSS in RMT and RMM) and biomass distribution patterns (30–35% in the feeding zone) at the end of the operation. Meanwhile, hydrogenotrophic methanogenesis mediated by Methanothermobacter coupled to syntrophic acetate oxidation prevailed in RMT, while the Methanosaeta-mediated acetoclastic pathway occurred in RMM. The results show that different anaerobic consortia can behave similarly in quantitative terms when subjected to equivalent organic loads, regardless of the prevailing methane-producing pathway. The community grows and reaches a balance (or a given cell activity level) defined by the amount of substrate available for conversion. In other words, while the metabolic pathway may differ, the endpoint (the amount of biomass) remains the same if operational stability is maintained.