When Should I Get My Next COVID-19 Vaccine? Data From the Surveillance of Responses to COVID-19 Vaccines in Systemic Immune-Mediated Inflammatory Diseases (SUCCEED) Study.

OBJECTIVE: To determine how serologic responses to coronavirus disease 2019 (COVID-19) vaccination and infection in immune-mediated inflammatory disease (IMID) are affected by time since last vaccination and other factors. METHODS: Post-COVID-19 vaccination, data, and dried blood spots or sera were collected from adults with rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis and spondylarthritis, and psoriasis and psoriatic arthritis. The first sample was collected at enrollment, then at 2 to 4 weeks and 3, 6, and 12 months after the latest vaccine dose. Multivariate generalized estimating equation regressions (including medications, demographics, and vaccination history) evaluated serologic response, based on log-transformed anti-receptor-binding domain (RBD) IgG titers; we also measured antinucleocapsid (anti-N) IgG. RESULTS: Positive associations for log-transformed anti-RBD titers were seen with female sex, number of doses, and self-reported COVID-19 infections in 2021 to 2023. Negative associations were seen with prednisone, anti-tumor necrosis factor agents, and rituximab. Over the 2021-2023 period, most (94%) of anti-N positivity was associated with a self-reported infection in the 3 months prior to testing. From March 2021 to February 2022, anti-N positivity was present in 5% to 15% of samples and was highest in the post-Omicron era, with antinucleocapsid positivity trending to 30% to 35% or higher as of March 2023. Anti-N positivity in IMID remained lower than Canada's general population seroprevalence (> 50% in 2022 and > 75% in 2023). Time since last vaccination was negatively associated with log-transformed anti-RBD titers, particularly after 210 days. CONCLUSION: Ours is the first pan-Canadian IMID assessment of how vaccine history and other factors affect serologic COVID-19 vaccine responses. These findings may help individuals personalize vaccination decisions, including consideration of additional vaccination when > 6 months has elapsed since last COVID-19 vaccination/infection.

Rab GTPases in Osteoclastic Bone Resorption and Autophagy.

Small guanosine triphosphate hydrolases (GTPases) of the Rab family are involved in plasma membrane delivery, fusion events, and lysosomal and autophagic degradation pathways, thereby regulating signaling pathways and cell differentiation and function. Osteoclasts are bone-resorbing cells that maintain bone homeostasis. Polarized vesicular trafficking pathways result in the formation of the ruffled border, the osteoclast's resorptive organelle, which also assists in transcytosis. Here, we reviewed the different roles of Rab GTPases in the endomembrane machinery of osteoclasts and in bone diseases caused by the dysfunction of these proteins, with a particular focus on autophagy and bone resorption. Understanding the molecular mechanisms underlying osteoclast-related bone disease development is critical for developing and improving therapies.

Influence of the TGF-ß Superfamily on Osteoclasts/Osteoblasts Balance in Physiological and Pathological Bone Conditions.

The balance between bone forming cells (osteoblasts/osteocytes) and bone resorbing cells (osteoclasts) plays a crucial role in tissue homeostasis and bone repair. Several hormones, cytokines, and growth factors-in particular the members of the TGF-ß superfamily such as the bone morphogenetic proteins-not only regulate the proliferation, differentiation, and functioning of these cells, but also coordinate the communication between them to ensure an appropriate response. Therefore, this review focuses on TGF-ß superfamily and its influence on bone formation and repair, through the regulation of osteoclastogenesis, osteogenic differentiation of stem cells, and osteoblasts/osteoclasts balance. After introducing the main types of bone cells, their differentiation and cooperation during bone remodeling and fracture healing processes are discussed. Then, the TGF-ß superfamily, its signaling via canonical and non-canonical pathways, as well as its regulation by Wnt/Notch or microRNAs are described and discussed. Its important role in bone homeostasis, repair, or disease is also highlighted. Finally, the clinical therapeutic uses of members of the TGF-ß superfamily and their associated complications are debated.

Chemical and odor characterization of gas emissions released during composting of solid wastes and digestates.

Hazardous and odorous gas emissions from composting and methanization plants are an issue of public concern. Odor and chemical monitoring are thus critical steps in providing suitable strategies for air pollution control at waste treatment units. In this study, 141 gas samples were extensively analyzed to characterize the odor and chemical emissions released upon the aerobic treatment of 10 raw substrates and five digestates. For this purpose, agricultural wastes, biowastes, green wastes, sewage sludge, and municipal solid waste (MSW) were composted in 300 L pilots under forced aeration. Gas exhausts were evaluated through dynamic olfactometry and analytical methods (i.e., GC/MS) to determine their odor concentration (OC in OUE m-3) and chemical composition. A total of 60 chemical compounds belonging to 9 chemical families were identified and quantified. Terpenes, oxygenated compounds, and ammonia exhibited the largest cumulative mass emission. Odor emission rates (OUE h-1) were computed based on OC measurements and related to the initial amount of organic matter composted and the process time to provide odor emission factors (OEFs in OUE g-1OM0). The composting process of solid wastes accounted for OEFs ranging from 65 to 3089 OUE g-1OM0, whereas digestates composting showed a lower odor emission potential with OEF fluctuating from 8.6 to 30.5 OUE g-1OM0. Moreover, chemical concentrations of single compounds were weighted with their corresponding odor detection thresholds (ODTs) to yield odor activities values (OAVs) and odor contribution (POi, %). Volatile sulfur compounds were the main odorants (POi = 54-99%) regardless of the operational composting conditions or substrate treated. Notably, methanethiol was the leading odorant for 73% of the composting experiments.

Understanding the anaerobic biodegradability of food waste: Relationship between the typological, biochemical and microbial characteristics.

In this study, an extensive characterisation of food waste (FW) was performed with the aim of studying the relation between FW characteristics and FW treatability through an anaerobic digestion process. In addition to the typological composition (paper, meat, fruits, vegetables contents, etc) and the physicochemical characteristics, this study provides an original characterisation of microbial populations present in FW. These intrinsic populations can actively participate to aerobic and anaerobic degradation with the presence of Proteobacteria and Firmicutes species for the bacteria and of Ascomycota phylum for the fungi. However, the characterisation of FW bacterial and fungi community shows to be a challenge because of the biases generated by the non-microbial DNA coming from plant and by the presence of mushrooms in the food. In terms of relations, it was demonstrated that some FW characteristics as the density, the volatile solids and the fibres content vary as a function of the typological composition. No direct relationship was demonstrated between the typological composition and the anaerobic biodegradability. However, the Pearson's matrix results reveal that the anaerobic biodegradation potential of FW was highly related to the total chemical oxygen demand (tCOD), the total solid content (TS), the high weight organic matter molecules soluble in water (SOLW>1.5 kDa) and the C/N ratio content. These relations may help predicting FW behaviour through anaerobic digestion process. Finally, this study also showed that the storage of FW before collection, that could induce pre-biodegradation, seems to impact several biochemical characteristics and could improve the biodegradability of FW.

Involvement of kinase PKC-zeta in the p62/p62(P392L)-driven activation of NF-κB in human osteoclasts.

Mutations of the gene encoding sequestosome1 (SQSTM1/p62), clustering in or near the UBA domain, have been described in Paget's disease of bone (PDB); among these the P392L substitution is the most prevalent. Protein p62 mediates several cell functions, including the control of NF-κB signaling, and autophagy. This scaffolding protein interacts with atypical PKCζ in the RANKL-induced signaling complex. We have previously shown that osteoclasts (OCs) overexpressing the p62(P392L) variant were in a constitutively activated state, presenting activated kinase p-PKCζ/λ and activated NF-κB prior to RANKL stimulation. In the present study, we investigated the relationships between PKCζ and NF-κB activation in human OCs transfected with p62 variants. We showed that PKCζ and p-PKCζ/λ co-localize with p62, and that PKCζ is involved in the RANKL-induced NF-κB activation and in the RANKL-independent activation of NF-κB observed in p62(P392L)-transfected cells. We also observed a basal and RANKL-induced increase in IκBα levels in the presence of the p62(P392L) mutation that contrasted with the NF-κB activation. In this study we propose that PKCζ plays a role in the activation of NF-κB by acting as a p65 (RelA) kinase at Ser(536), independently of IκBα; this alternative pathway could be used preferentially in the presence of the p62(P392L) mutation, which may hinder the ubiquitin-proteasome pathway. Overall, our results highlight the importance of p62-associated PKCζ in the overactive state of pagetic OCs and in the activation of NF-κB, particularly in the presence of the p62(P392L) mutation.

Alternative splicing in osteoclasts and Paget's disease of bone.

BACKGROUND: Mutations in the SQSTM1/p62 gene have been reported in Paget's disease of bone (PDB), but they are not sufficient to induce the pagetic osteoclast (OC) phenotype. We hypothesized that specific RNA isoforms of OC-related genes may contribute to the overactivity of pagetic OCs, along with other genetic predisposing factors. METHODS: Alternative splicing (AS) events were studied using a PCR-based screening strategy in OC cultures from 29 patients with PDB and 26 healthy donors (HD), all genotyped for the p62P392L mutation. Primer pairs targeting 5223 characterized AS events were used to analyze relative isoform ratios on pooled cDNA from samples of the four groups (PDB, PDBP392L, HD, HDP392L). Of the 1056 active AS events detected in the screening analysis, 192 were re-analyzed on non-amplified cDNA from each subject of the whole cohort. RESULTS: This analysis led to the identification of six AS events significantly associated with PDB, but none with p62P392L. The corresponding genes included LGALS8, RHOT1, CASC4, USP4, TBC1D25, and PIDD. In addition, RHOT1 and LGALS8 genes were upregulated in pagetic OCs, as were CASC4 and RHOT1 genes in the presence of p62P392L. Finally, we showed that the proteins encoded by LGALS8, RHOT1, USP4, TBC1D25, and PIDD were expressed in human OCs. CONCLUSION: This study allowed the identification of hitherto unknown players in OC biology, and our findings of a differential AS in pagetic OCs may generate new concepts in the pathogenesis of PDB.

Galectin-8 modulates human osteoclast activity partly through isoform-specific interactions.

In overactive human osteoclasts, we previously identified an alternative splicing event in LGALS8, encoding galectin-8, resulting in decreased expression of the long isoform. Galectin-8, which modulates cell-matrix interactions and functions intracellularly as a danger recognition receptor, has never been associated with osteoclast biology. In human osteoclasts, inhibition of galectin-8 expression revealed its roles in bone resorption, osteoclast nuclearity, and mTORC1 signaling regulation. Galectin-8 isoform-specific inhibition asserted a predominant role for the short isoform in bone resorption. Moreover, a liquid chromatography with tandem mass spectrometry (LC-MS/MS) proteomic analysis of galectin-8 isoforms performed in HEK293T cells identified 22 proteins shared by both isoforms. Meanwhile, nine interacting partners were specific for the short isoform, and none were unique to the long isoform. Interactors specific for the galectin-8 short isoform included cell adhesion proteins and lysosomal proteins. We confirmed the interactions of galectin-8 with CLCN3, CLCN7, LAMP1, and LAMP2, all known to localize to secretory vesicles, in human osteoclasts. Altogether, our study reveals direct roles of galectin-8 in osteoclast activity, mostly attributable to the short isoform.

Microsecond fiber laser pumped, single-frequency optical parametric oscillator for trace gas detection.

We report on the first microsecond doubly resonant optical parametric oscillator (OPO). It is based on a nested cavity OPO architecture allowing single longitudinal mode operation and low oscillation threshold (few microjoule). The combination with a master oscillator-power amplifier fiber pump laser provides a versatile optical source widely tunable in the 3.3-3.5 µm range with an adjustable pulse repetition rate (from 40 to 100 kHz), high duty cycle (~10(-2)) and mean power (up to 25 mW in the idler beam). The potential for trace gas sensing applications is demonstrated through photoacoustic detection of atmospheric methane.

SARS-CoV-2 mRNA vaccine-induced immune responses in rheumatoid arthritis.

Our objective was to characterize T and B cell responses to vaccination with SARS-CoV-2 antigens in immunocompromised rheumatoid arthritis (RA) patients. In 22 RA patients, clinical and biological variables were analyzed before and 4 weeks after each of 3 messenger RNA (mRNA) vaccine doses and compared with unmatched healthy individuals. Sequentially sampled peripheral blood mononuclear cells and sera were collected to determine immune profiles and to analyze the T cell response to a spike peptide pool and B cell specificity to the receptor-binding domain (RBD). Anti-spike antibodies were detectable in 6 of 22 RA patients after 1 dose of vaccine with increasing titers after each booster dose, although the overall response was lower compared with that in healthy control individuals. Responding patients after the first dose were more likely to have RA antibodies and a higher baseline proportion of circulating follicular B cells. In RA patients, the mRNA vaccine elicited a robust CD4+ T response to a spike peptide pool following the first and second doses. Consistent with the serologies, RBD-specific B cells exhibited a modest increase after the first dose and the second dose resulted in marked increases only in a fraction of the RA patients to both ancestral and omicron RBD. Our results highlight the importance of multidose COVID-19 vaccination in RA patients to develop a protective humoral response. However, these patients rapidly develop specific T CD4+ responses, despite delayed B cell responses.

Quantification of indicator and pathogenic bacteria in manures and digestates from three agricultural biogas plants over a one-year period.

Interest in the conversion of manure in biogas via anaerobic digestion (AD) is growing, but questions remain about the biosafety of digestates. For a period of one year, we monitored the impact of three mesophilic agricultural biogas plants (BPs) mainly fed with pig manure (BP1, BP3) or bovine manure (BP2) on the physicochemical parameters, the composition of the microbial community and the concentration of bacteria (E. coli, enterococci, Salmonella, Campylobacter, Listeria monocytogenes, Clostridium perfringens, Clostridium botulinum and Clostridioides difficile). The BP2 digestate differed from those of the two other BPs with a higher nitrogen content, more total solids and greater abundance of Clostridia MBA03 and Disgonomonadacea. Persistence during digestion ranked from least to most, was: Campylobacter (1.6 to >2.9 log10 reduction, according to the BP) < E. coli (1.8 to 2.2 log10) < Salmonella (1.1 to 1.4 log10) < enterococci (0.2 to 1.2 log10) and C. perfringens (0.2 to 1 log10) < L. monocytogenes (-1.2 to 1.6 log10) < C. difficile and C. botulinum (≤0.5 log10). No statistical link was found between the reduction in the concentration of the targeted bacteria and the physicochemical and operational parameters likely to have an effect (NH3, volatile fatty acids and total solids contents, hydraulic retention time, presence of co-substrates), underlining the fact that the fate of the bacteria during mesophilic digestion depends on many interacting factors. The reduction in concentrations varied significantly over the sampling period, underlining the need for longitudinal studies to estimate the impact of AD on pathogenic microorganisms.

Modulation of tumor necrosis factor related apoptosis-inducing ligand (TRAIL) receptors in a human osteoclast model in vitro.

TRAIL (TNF-related apoptosis-inducing ligand) has been shown to induce apoptosis by binding to TRAIL-R1 and -R2 death receptors, but not to TRAIL-R3 or -R4, its decoy receptors that lack the internal death domain. Osteoclasts (Ocs) are sensitive to TRAIL-induced apoptosis, and modulation of these receptors may change Oc sensitivity to TRAIL. Using human Oc cultures, we first investigated the gene expression profile of these receptors (TNFRSF10 -A, -B, -C, -D encoding TRAIL-Rs 1-4) by real time PCR after adding osteotropic factors during the last week of Oc cultures. We observed a significant decrease in the expression of TNFRSF10-A after the addition of TGFß, and an increase in that of TNFRSF10-A and -B post-PTH stimulation. Protein expression of TRAIL-R1 and -R3 was upregulated in the presence of MIP-1α, but down-regulated in the presence of TGFß (R1), TRAIL (R2) or OPG (R3). The percentage of Ocs expressing the TRAIL-R1 and/or -R2 at their surface was increased by MIP-1α and TRAIL, increased (R2) or decreased (R1) by TGFß, and the percentage expressing TRAIL-R3 was increased by MIP-1α, TRAIL and RANKL. Although significant, the magnitude of all these changes was of about 10-15%. While a direct correlation between these changes and TRAIL-induced Oc apoptosis was less clear, a protective effect was observed in Ocs that had been treated with OPG, and an additive effect in Ocs pre-treated with TRAIL or TGFß increased TRAIL sensitivity.

Low-temperature atmospheric pressure argon plasma treatment and hybrid laser-plasma ablation of barite crown and heavy flint glass.

We report on atmospheric pressure argon plasma-based surface treatment and hybrid laser-plasma ablation of barite crown glass N-BaK4 and heavy flint glass SF5. By pure plasma treatment, a significant surface smoothing, as well as an increase in both the surface energy and the strength of the investigated glass surfaces, was achieved. It was shown that for both glasses, hybrid laser plasma ablation allows an increase in the ablation depth by a factor of 2.1 with respect to pure laser ablation. The ablated volume was increased by an averaged factor of 1.5 for N-BaK4 and 3.7 for SF5.

Mindfulness-based stress reduction to improve depression, pain and high patient global assessment in controlled rheumatoid arthritis.

Objective: The aim was to improve distressing patient-reported outcomes (PROs) that persisted in RA patients with clinically controlled inflammation (controlled RA). Methods: In a pragmatic pilot study, we offered mindfulness-based stress reduction (MBSR), a group intervention, to controlled RA patients who had high (≥16) Centre for Evaluation Studies depression (CES-D) scores and/or patient general assessment of disease activity (PGA) at least 2/10 larger than evaluator general assessment (EGA) (PGA-EGA: Delta). Evaluations before, 6 and 12 months after MBSR included CES-D, PGA, modified HAQ, simple disease activity index (SDAI), anxiety (general anxiety disorder 7; GAD-7), coping strategies (coping with health injuries and problems; CHIP), sleep disturbance and pain. Facilitators and obstacles to recruitment and participation were identified. A subset of patients was interviewed for qualitative analysis of their experience. Results: Out of 306 screened patients, 65 were referred, 39 (60%) agreed and 28 (43%) completed MBSR. Anticipated burden, timing and frequency of group meetings, commuting issues, age extremes and co-morbidities were barriers to participation. Up to 12 months after MBSR, anxiety, depression, emotion-oriented coping, sleep and function significantly improved. Nonetheless, no significant impact was observed on pain, PGA, Delta or SDAI. The interviews revealed that benefits, including integration of effective coping strategies, were maintained. Conclusion: We addressed MBSR feasibility issues and selection of outcomes in controlled RA patients with distressing PROs. For patients who chose to participate in MBSR, lasting benefits were evident for anxiety, depression, sleep and function. Larger studies are required to evaluate the weaker impact of MBSR on RA-related pain and PGA.

TRPV-5 mediates a receptor activator of NF-kappaB (RANK) ligand-induced increase in cytosolic Ca2+ in human osteoclasts and down-regulates bone resorption.

Most of the signaling effectors located downstream of receptor activator of NF-kappaB (RANK) activation are calcium-sensitive. However, the early signaling events that lead to the mobilization of intracellular calcium in human osteoclasts are still poorly understood. The Ca(2+)-sensitive fluorescent probe Fura2 was used to detect changes in the intracellular concentration of Ca(2+) ([Ca(2+)](i)) in a model of human osteoclasts. Stimulating these cells with receptor activator of NF-kappaB ligand (RANKL) induced a rapid and significant increase in [Ca(2+)](i). Adding extracellular Ca(2+) chelators, depleting intracellular stores, and the use of a phospholipase C inhibitor all indicated that the Ca(2+) was of extracellular origin, suggesting the involvement of a Ca(2+) channel. We showed that none of the classical Ca(2+) channels (L-, T-, or R-type) were involved in the RANKL-induced Ca(2+) spike. However, the effect of high doses of Gd(3+) did suggest that TRP family channels were present in human osteoclasts. The TRPV-5 channel was expressed in osteoclasts and was mainly located in the cellular area in contact with the bone surface. Furthermore, the RNA inactivation of TRPV-5 channel completely inhibited the RANKL-induced increase in [Ca(2+)](i), which was accompanied in the long term by marked activation of bone resorption. Overall, our results show that RANKL induced a significant increase in [Ca(2+)](i) of extracellular origin, probably as a result of the opening of TRPV-5 calcium channels on the surface of human osteoclasts. Our findings suggest that TRPV-5 contributes to maintaining the homeostasis of the human skeleton via a negative feedback loop in RANKL-induced bone resorption.

RabGAP TBC1D25 is involved in human osteoclast activity.

The osteoclast cell polarization and the ruffled border formation during bone resorption are major vesicle trafficking events. Rab GTPases have been shown to be involved in these processes, however very little is known about their regulators, such as Rab GTPase activating proteins (RabGAPs). In osteoclasts, we previously identified two spliced isoforms of TBC1D25, encoding a RabGAP which had never been studied in these cells. Using in vitro cultures, we evaluated the expression of TBC1D25 in human osteoclasts. TBC1D25 was expressed at the sealing zone co-localizing with F-actin, with an annular distribution, and also at the ruffled membrane with a less intense colocalization with LAMP2 and cathepsin K, but none with Rab7 or V-ATPase. Inhibiting TBC1D25 expression significantly decreased bone resorption, as well as the formation of multinucleated cells and the number of nuclei per cell. These results suggest that TBC1D25 has a role in bone resorption via the regulation of osteoclast polarization and resorption, and multinucleation as well.

miR profile in pagetic osteoclasts: from large-scale sequencing to gene expression study.

Paget's disease of bone (PDB) is characterized by excessive and disorganized bone remodeling, in which bone-resorbing osteoclasts play a key role. We investigated microRNA (miR) expression in osteoclasts derived from the blood of 40 PDB patients and 30 healthy controls. By deep sequencing, a preliminary analysis identified differentially expressed miRs in a discovery cohort of 9 PDB patients and 9 age and sex-matched healthy controls. Six mature miRs, miR-29b1-3p, miR-15b-5p, miR-181a-5p, let-7i-3p, miR-500b-5p, and miR-1246, were found to be significantly decreased in pagetic overactive osteoclasts. The differential expression of the miRs was confirmed by the analysis of a larger independent cohort using qPCR. In an integrative network biology analysis of the miR candidates, we identified strong validated interactions between the miRs and some pathways, primarily apoptosis, and major osteoclast signaling pathways including PI3K/Akt, IFNγ, or TGFß, as well as c-Fos, a transcription factor, and MMP-9, a metalloprotease. In addition, other genes like CCND2, CCND1, WEE1, SAMHD1, and AXIN2 were revealed in this network of interactions. Our results enhance the understanding of osteoclast biology in PDB; our work may also provide fresh perspectives on the research or therapeutic development of other bone diseases. KEY MESSAGES: miR profile in overactive osteoclasts from patients with Paget's disease of bone. Six mature miRs were significantly decreased in pagetic osteoclasts vs controls. miRs of interest: let7i-3p, miR-15b-5p, -29b1-3p, -181a-5p, -500b-5p, and -1246. Target genes and enriched pathways highlight the importance of apoptotic pathways.

Impending radiographic erosive progression over the following year in a cohort of consecutive patients with inflammatory polyarthritis: prediction by serum biomarkers.

BACKGROUND/PURPOSE: To evaluate biomarkers as predictors of impending erosion progression. METHODS: Variables were measured at baseline and annually up to 5 years in patients with recent-onset polyarthritis treated to zero swollen joints. Erosive status was defined as ≥5 Units in Sharp/van der Heijde Erosion Score; Rapid Erosive Progression (REP) was defined as an increase ≥5 Units in Erosion Scores between consecutive visits. Generalised estimating equations (GEEs) evaluated the effect on REP of positive anticyclic citrullinated peptides (ACPAs) and/or rheumatoid factor (RF), C-reactive protein ˃8.0 mg/L (High-CRP) and 14-3-3η protein ≥0.50 ng/mL (High-14-3-3η), alone and in combinations. RESULTS: Out of 2155 evaluations in 749 consecutive patients, REP occurred after 186 (8.6%) visits, including 13 (2.2%) in patients recruited since 2010. Only 18/537 (3.4%; 6/411 (1.5%) in non-erosive vs 12/126 (9.5%) in patients already erosive) visits without any positive biomarker were followed by REP; at least one biomarker was positive prior to REP in 168/186 (90.3%) visits. Being positive for all four biomarkers conferred a positive predictive value (PPV) of 30.0% (RR 21.8) in patients non-erosive at the visit versus 35.5% (RR 3.07) in those already erosive. High-14-3-3η increased REP only in visits with High-CRP (eg, RR 2.5 to 3.9 when ACPA also positive) and in patients with non-erosive status (eg, RR from 4.3 to 9.4 when also High-CRP). CONCLUSIONS: Adding High-14-3-3η to positive antibodies and CRP improves prediction of impending REP. Although REP is becoming rarer, signatures of biomarkers might help to adapt treatment strategies in at-risk individuals, even those already erosive.

Osteoclast signaling-targeting miR-146a-3p and miR-155-5p are downregulated in Paget's disease of bone.

MicroRNA (miRs) are small, non-coding RNA that post-transcriptionally regulate DNA expression. We hypothesized that specific miR profiles may be a feature of overactive osteoclasts in Paget's disease of bone (PDB), a disorder characterized by an increased and disorganized bone remodeling that typically begins with excessive bone resorption. We compared the expression profile of 13 miRs in human osteoclasts differentiated in vitro from peripheral blood mononuclear cells (PBMCs) of patients with PDB (n = 10) or age- and sex- matched healthy subjects (n = 10). We selected 13 miRs for testing, on the basis of their previously reported roles either in human osteoclast differentiation, in bone diseases, or in osteoclast important signaling pathways. From those expression results, 3 miRNAs were further selected for in-vitro studies aiming at modulating miR expression in human cord blood monocyte derived osteoclasts: 2 miRs (miR-146a-3p and miR-155-5p) whose expression was significantly reduced in pagetic osteoclasts, as well as miRNA-133a-3p, stable in PDB relative to controls, but with known regulatory importance within osteoclasts. We demonstrated a positive (miR-133a-3p) or negative (miR-155-5p, miR-146a-3p) impact of those miRs on the formation of osteoclasts and/or their bone resorption capacity in this human model. Signaling pathways were significantly affected, including p38 MAP-kinase (miR-133a-3p), RANKL-induced TRAF6/NFκB signaling (miR-146a-3p), and MITF expression (miR-155-5p). Osteoclast miRNA profiles might have an important value to yield significant new insights into the osteoclast phenotype in PDB and in other bone diseases with hyperactive osteoclasts.

Effect of starvation period on microbial community producing hydrogen from paperboard mill wastewater using anaerobic baffled reactor.

The aim of this study is to highlight the robustness and potentials of the anaerobic baffled reactor (ABR) configuration on keeping the microbial richness and diversity after starvation period of 7 days. The module at steady state operating conditions provided an average volumetric hydrogen production (VHP) of 0.2 ± 0.08 and 0.423 ± 0.5 l/d in the 1st and last compartment (C4). The VHP was gradually decreased from 0.2 to 0.003 l/d and from 0.423 to 0.1 l/d in compartments (C1 and C4) respectively during feed less period. However, the VHP was substantially increased up to 0.035 and 0.152 l/d in 1st (C1) and fourth compartment (C4) within 24 h, after reoperation of the ABR. Moreover, the H2 producers of Clostridiaceae, Ruminococcaceae, and Enterobacteriaceae families were dominant in the reactor after reoperation process. Quantitative polymerase chain reaction and next-generation sequencing methods results revealed that the microbial community structure was mainly composed of Proteobacteria, Firmicutes, Chloroflexi, Bacteroidetes, Planctomycetes, and Actinobacteria. The results showed the unique properties of the ABR configuration for keeping the microbial richness and diversity during feed less period.