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1. Spatial Gradients of Quantitative MRI as Biomarkers for Early Detection of Osteoarthritis: Data From Human Explants and the Osteoarthritis Initiative

   https://doi.org/10.1002/jmri.28471  

   Wilson, Robert L. ; Emery, Nancy C. ; Pierce, David M. ; Neu, Corey P. ( October 2022 , Journal of Magnetic Resonance Imaging)

   Healthy articular cartilage presents structural gradients defined by distinct zonal patterns through the thickness, which may be disrupted in the pathogenesis of several disorders. Analysis of textural patterns using quantitative MRI data may identify structural gradients of healthy or degenerating tissue that correlate with early osteoarthritis (OA).

   To quantify spatial gradients and patterns in MRI data, and to probe new candidate biomarkers for early severity of OA.

   Retrospective study.

   Fourteen volunteers receiving total knee replacement surgery (eight males/two females/four unknown, average age ± standard deviation: 68.1 ± 9.6 years) and 10 patients from the OA Initiative (OAI) with radiographic OA onset (two males/eight females, average age ± standard deviation: 57.7 ± 9.4 years; initial Kellgren‐Lawrence [KL] grade: 0; final KL grade: 3 over the 10‐year study).

   3.0‐T and 14.1‐T, biomechanics‐based displacement‐encoded imaging, fast spin echo, multi‐slice multi‐echoT2mapping.

   We studied structure and strain in cartilage explants from volunteers receiving total knee replacement, or structure in cartilage of OAI patients with progressive OA. We calculated spatial gradients of quantitative MRI measures (eg, T2) normal to the cartilage surface to enhance zonal variations. We compared gradient values against histologically OA severity, conventional relaxometry, and/or KL grades.

   Multiparametric linear regression for evaluation of the relationship between residuals of the mixed effects models and histologically determined OA severity scoring, with a significance threshold atα = 0.05.

   Gradients of individual relaxometry and biomechanics measures significantly correlated with OA severity, outperforming conventional relaxometry and strain metrics. In human explants, analysis of spatial gradients provided the strongest relationship to OA severity (R² = 0.627). Spatial gradients of T2 from OAI data identified variations in radiographic (KL Grade 2) OA severity in single subjects, while conventional T2 alone did not.

   Spatial gradients of quantitative MRI data may improve the predictive power of noninvasive imaging for early‐stage degeneration.

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2. Binge Drinking Decreases Corticotropin‐Releasing Factor‐Binding Protein Expression in the Medial Prefrontal Cortex of Mice

   https://doi.org/10.1111/acer.13119  

   Ketchesin, Kyle D. ; Stinnett, Gwen S. ; Seasholtz, Audrey F. ( July 2016 , Alcoholism: Clinical and Experimental Research)

   Dysregulation of the corticotropin‐releasing factor (CRF) system has been observed in rodent models of binge drinking, with a large focus onCRFreceptor 1 (CRF‐R1). The role ofCRF‐binding protein (CRF‐BP), a key regulator ofCRFactivity, in binge drinking is less well understood. In humans, single‐nucleotide polymorphisms inCRHBPare associated with alcohol use disorder and stress‐induced alcohol craving, suggesting a role forCRF‐BPin vulnerability to alcohol addiction.

   The role and regulation ofCRF‐BPin binge drinking were examined in mice exposed to the drinking in the dark (DID) paradigm. Using in situ hybridization, the regulation ofCRF‐BP,CRF‐R1, andCRFmRNAexpression was determined in the stress and reward systems of C57BL/6J mice after repeated cycles ofDID. To determine the functional role ofCRF‐BPin binge drinking,CRF‐BPknockout (CRF‐BP KO) mice were exposed to 6 cycles ofDID, during which alcohol consumption was measured and compared to wild‐type mice.

   CRF‐BPmRNAexpression was significantly decreased in the prelimbic (PL) and infralimbic medial prefrontal cortex (mPFC) of C57BL/6J mice after 3 cycles and in thePLmPFCafter 6 cycles ofDID. No significant changes inCRForCRF‐R1 mRNAlevels were observed in mPFC, ventral tegmental area, bed nucleus of the stria terminalis, or amygdala after 3 cycles ofDID.CRF‐BP KOmice do not show significant alterations in drinking compared to wild‐type mice across 6 cycles of DID.

   These results reveal that repeated cycles of binge drinking alterCRF‐BPmRNAexpression in the mPFC, a region responsible for executive function and regulation of emotion and behavior, including responses to stress. We observed a persistent decrease inCRF‐BPmRNAexpression in the mPFCafter 3 and 6DIDcycles, which may allow for increasedCRFsignaling atCRF‐R1 and contribute to excessive binge‐like ethanol consumption.

    

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3. Mechanosensitive Control of Articular Cartilage and Subchondral Bone Homeostasis in Mice Requires Osteocytic Transforming Growth Factor β Signaling

   https://doi.org/10.1002/art.41548  

   Bailey, Karsyn N. ; Nguyen, Jeffrey ; Yee, Cristal S. ; Dole, Neha S. ; Dang, Alexis ; Alliston, Tamara ( February 2021 , Arthritis & Rheumatology)

   Transforming growth factor β (TGFβ) signaling plays a complex tissue‐specific and nonlinear role in osteoarthritis (OA). This study was conducted to determine the osteocytic contributions of TGFβ signaling to OA.

   To identify the role of osteocytic TGFβ signaling in joint homeostasis, we used 16‐week‐old male mice (n = 9–11 per group) and female mice (n = 7–11 per group) with an osteocyte‐intrinsic ablation of TGFβ receptor type II (TβRII^ocy−/−mice) and assessed defects in cartilage degeneration, subchondral bone plate (SBP) thickness, and SBP sclerostin expression. To further investigate these mechanisms in 16‐week‐old male mice, we perturbed joint homeostasis by subjecting 8‐week‐old mice to medial meniscal/ligamentous injury (MLI), which preferentially disrupts the mechanical environment of the medial joint to induce OA.

   In all contexts, independent of sex, genotype, or medial or lateral joint compartment, increased SBP thickness and SBP sclerostin expression were spatially associated with cartilage degeneration. Male TβRII^ocy−/−mice, but not female TβRII^ocy−/−mice, had increased cartilage degeneration, increased SBP thickness, and higher levels of SBP sclerostin compared with control mice (allP< 0.05), demonstrating that the role of osteocytic TGFβ signaling on joint homeostasis is sexually dimorphic. With changes in joint mechanics following injury, control mice had increased SBP thickness, subchondral bone volume, and SBP sclerostin expression (allP< 0.05). TβRII^ocy−/−mice, however, were insensitive to subchondral bone changes with injury, suggesting that mechanosensation at the SBP requires osteocytic TGFβ signaling.

   Our results provide new evidence that osteocytic TGFβ signaling is required for a mechanosensitive response to injury, and that osteocytes control SBP homeostasis to maintain cartilage health, identifying osteocytic TGFβ signaling as a novel therapeutic target for OA.

    

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4. Changes in stable isotope compositions during fasting in phocid seals

   https://doi.org/10.1002/rcm.8308  

   Habran, Sarah ; Damseaux, France ; Pomeroy, Paddy ; Debier, Cathy ; Crocker, Daniel ; Lepoint, Gilles ; Das, Krishna ( December 2018 , Rapid Communications in Mass Spectrometry)

   The grey seal,Halichoerus grypus(GS), and the northern elephant seal,Mirounga angustirostris(NES), come ashore for reproduction. This period involves intense physiological processes such as lactation in females and a developmental post‐weaning fast in juveniles. Previous studies have shown thatδ¹³C andδ¹⁵N values are affected by starvation, but the precise effects of fasting associated with lactation and post‐weaning fast in seals remain poorly understood.

   To examine the effect of lactation and post‐weaning fast on stable isotope ratios in GS and NES, blood and hair were sampled from 21 GS mother‐pup pairs on the Isle of May and on 22 weaned NES pups at Año Nuevo State Reserve during their respective breeding seasons. Milk samples were also collected from GS mothers. Stable isotope measurements were performed with an isotope ratio mass spectrometer coupled to an N‐C elemental analyser.

   Changes in stable isotope ratios in blood components during fasting were similar and weak between GS and NES mothers especially in blood cells (GS:Δ¹⁵N = 0.05‰,Δ¹³C = 0.02‰; NES:Δ¹⁵N = 0.1‰,Δ¹³C = 0.1‰). GS showed a¹⁵N discrimination factor between maternal and pup blood cells and milk, but not for¹³C. The strongest relationship between the isotopic compositions of the mother and the pup was observed in the blood cells.

   Isotopic consequences of lactation, fasting, and growth seem limited in NES and GS, especially in medium‐term integrator tissues of feeding activity such as blood cells. Stable isotope ratios in the blood of pups and mothers are correlated. We observed a subtle mother‐to‐pup fractionation factor. Our results suggest that pup blood cells are mostly relevant for exploring the ecology of female seals.

    

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5. Effects of external recirculation on a two‐stage mainstream anaerobic‐anammox treatment system

   https://doi.org/10.1002/wer.1019  

   Li, Xiaojin ; He, Zhen ( February 2019 , Water Environment Research)

   Nitritation‐anammox treatment can be a potentially energy‐ and resource‐efficient technology for treating mainstream wastewater. However, the issue of nitrate residue from anammox treatment remains to be addressed. Herein, external recirculation of the anammox effluent to a hybrid anaerobic reactor (HAR), which was also to provide a continuous flow with lowCOD/N for the nitritation‐anammox reactor, was employed to decrease the residue compounds. The recirculation ratio of 50% was observed to be the optimal to achieve the best overall performance with potential savings in energy demand. Specifically, in the operation scenario ofR = 50%, the highestCODremoval of ~90% by theHARwas achieved. Meanwhile, the lowestCOD/NH₄⁺‐N ratio of ~2.0 in theHAReffluent ensured the lowest observedNO₃⁻‐N/NH₄⁺‐N ratio of ~14% in the nitritation‐anammox reactor. These results have demonstrated the feasibility of applying external recirculation for nitrate residue removalviadenitrification in the anaerobic pretreatment stage.

   Nitritation‐anammox treatment is an attractive method for mainstream wastewater treatment.

   Nitrate residue from anammox processes contributes to total nitrogen in the final effluent.

   Recirculation of anammox effluent to an anaerobic reactor can decrease nitrate residue.

   A recirculation ratio of 50% results in a low COD/NH₄⁺ratio of 2 that benefits the subsequent anammox.

    

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