Associations among serum pro- and anti-inflammatory cytokines, metabolic mediators, body condition, and uterine disease in postpartum dairy cows

BACKGROUND: Adipose tissue is an active endocrine organ which secretes a wide range of hormones and protein factors, collectively termed adipokines. Adipokines affect appetite and satiety, glucose and lipid metabolism, inflammation and immune functions. The objectives were to evaluate serum concentrations of adipokines (adiponectin, leptin, tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6) in lactating dairy cows with postpartum uterine inflammatory conditions (metritis, clinical endometritis or subclinical endometritis) and in cows experiencing loss of body condition, and to assess the relationship of adipokines and body condition loss in the establishment of persistent uterine inflammatory conditions. METHODS: Lactating multiparous Holstein cows (N = 40), with body condition scores (BCS) from 2 to 4 (eight cows for each 0.5 score increment) were enrolled. Body condition was monitored for all cows weekly for 7 weeks post calving; cows with uterine inflammatory conditions were also re-evaluated 2 weeks later. Blood samples were collected from 1 week prior to calving to 7 weeks after calving for determination of serum concentrations of adipokines, insulin and insulin like growth factor (IGF)-1. RESULTS: Cows with metritis or clinical endometritis had higher serum concentrations of adiponectin, leptin, TNF-alpha, IL-1beta and IL-6 compared to normal cows (P < 0.05). Furthermore, serum leptin, TNF-alpha, IL-1beta and IL-6 were higher in cows with subclinical endometritis compared to normal cows (P < 0.05), and insulin and IGF-1 concentrations were lower in cows with metritis or clinical endometritis. Cows with low BCS (2 and 2.5) had significantly higher adiponectin, TNF-alpha, IL-1beta and IL-6 than those with high BCS (3 to 4). Cows with persistent uterine inflammatory conditions had higher adiponectin, leptin TNF-alpha, IL-1beta and IL-6 and insulin compared to normal and spontaneously recovered cows, except for IGF-1 (P < 0.05). CONCLUSIONS: Serum concentrations of adipokines, insulin, and IGF-1 had significant associations with BCS categories (low vs. high) and postpartum uterine inflammatory conditions. Perhaps loss of body condition mediated increases in anti- and pro-inflammatory cytokines, whereas increased pro- and anti-inflammatory cytokines concentrations mediated body condition loss and thereby prolonged persistence of uterine inflammation in dairy cows

Phosphorylation of the ribosomal protein RPL12/uL11 affects translation during mitosis

Emerging evidence indicates that heterogeneity in ribosome composition can give rise to specialized functions. Until now, research mainly focused on differences in core ribosomal proteins and associated factors. The effect of posttranslational modifications has not been studied systematically. Analyzing ribosome heterogeneity is challenging because individual proteins can be part of different subcomplexes (40S, 60S, 80S, and polysomes). Here we develop polysome proteome profiling to obtain unbiased proteomic maps across ribosomal subcomplexes. Our method combines extensive fractionation by sucrose gradient centrifugation with quantitative mass spectrometry. The high resolution of the profiles allows us to assign proteins to specific subcomplexes. Phosphoproteomics on the fractions reveals that phosphorylation of serine 38 in RPL12/uL11, a known mitotic CDK1 substrate, is strongly depleted in polysomes. Follow-up experiments confirm that RPL12/uL11 phosphorylation regulates the translation of specific subsets of mRNAs during mitosis. Together, our results show that posttranslational modification of ribosomal proteins can regulate translation

Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat

Knockout of the ubiquitously expressed miRNA-17~92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17~92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17~92:Bim interactions to the complex miR-17~92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17~92 seed matches. Blocking miR-17~92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17~92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17~92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts

Traumatic Stress Interacts With Bipolar Disorder Genetic Risk to Increase Risk for Suicide Attempts

Objective Bipolar disorder (BD) is one of the most heritable psychiatric conditions and is associated with high suicide risk. To explore the reasons for this link, this study examined the interaction between traumatic stress and BD polygenic risk score in relation to suicidal ideation, suicide attempt, and nonsuicidal self-injury (NSSI) in adolescent and young adult offspring and relatives of persons with BD (BD-relatives) compared with adolescent and young adult offspring of individuals without psychiatric disorders (controls). Method Data were collected from 4 sites in the United States and 1 site in Australia from 2006 through 2012. Generalized estimating equation models were used to compare rates of ideation, attempts, and NSSI between BD-relatives (n = 307) and controls (n = 166) and to determine the contribution of demographic factors, traumatic stress exposure, lifetime mood or substance (alcohol/drug) use disorders, and BD polygenic risk score. Results After adjusting for demographic characteristics and mood and substance use disorders, BD-relatives were at increased risk for suicidal ideation and attempts but not for NSSI. Independent of BD-relative versus control status, demographic factors, or mood and substance use disorders, exposure to trauma within the past year (including bullying, sexual abuse, and domestic violence) was associated with suicide attempts (p = .014), and BD polygenic risk score was marginally associated with attempts (p = .061). Importantly, the interaction between BD polygenic risk score and traumatic event exposures was significantly associated with attempts, independent of demographics, relative versus control status, and mood and substance use disorders (p = .041). Conclusion BD-relatives are at increased risk for suicide attempts and ideation, especially if they are exposed to trauma and have evidence of increased genetic vulnerability

Monitoraggio in area sismica di beni monumentali: tecniche NDT e procedure di verifica

Negli ultimi anni il concetto di vulnerabilità sismica è tristemente entrato a far parte delle conoscenze anche dei non addetti ai lavori. Infatti, gli eventi sismici che hanno interessato dagli inizi del ‘900 il territorio Italiano, hanno sistematicamente messo in risalto l’elevata vulnerabilità sismica del nostro patrimonio edilizio, ivi compresi i beni monumentali, nonché, l’inesistenza di qualsiasi attività di programmazione della manutenzione periodica ordinaria e straordinaria delle strutture sismo-resistenti, che garantiscono nel tempo la conservazione delle loro capacità di risposta alle perturbazioni esterne.Il progetto PON sul Monitoraggio in Area Sismica di SIstemi MOnumentali nasce con la prerogativa di produrre uno strumento dedicato alla tutela di strutture a valenza storico – artistica, attraverso un percorso di catalogazione, di analisi del bene inteso come elemento costituito da elementi resistenti e da materiali, di studio del sito dove la struttura è ubicata e di attività di monitoraggio

Laser-induced modification of the patellar ligament tissue: comparative study of structural and optical changes

The effects of non-ablative infrared (IR) laser treatment of collagenous tissue have been commonly interpreted in terms of collagen denaturation spread over the laser-heated tissue area. In this work, the existing model is refined to account for the recently reported laser-treated tissue heterogeneity and complex collagen degradation pattern using comprehensive optical imaging and calorimetry toolkits. Patella ligament (PL) provided a simple model of type I collagen tissue containing its full structural content from triple-helix molecules to gross architecture. PL ex vivo was subjected to IR laser treatments (laser spot, 1.6 mm) of equal dose, where the tissue temperature reached the collagen denaturation temperature of 60 ± 2°C at the laser spot epicenterin the first regime, and was limited to 67 ± 2°C in the second regime. The collagen network was analyzed versus distance from the epicenter. Experimental characterization of the collagenous tissue at all structural levels included cross-polarization optical coherence tomography, nonlinear optical microscopy, light microscopy/histology, and differential scanning calorimetry. Regressive rearrangement of the PL collagen network was found to spread well outside the laser spot epicenter (>2 mm) and was accompanied by multilevel hierarchical reorganization of collagen. Four zones of distinct optical and morphological properties were identified, all elliptical in shape, and elongated in the direction perpendicular to the PL long axis. Although the collagen transformation into a random-coil molecular structure was occasionally observed, it was mechanical integrity of the supramolecular structures that was primarily compromised. We found that the structural rearrangement of the collagen network related primarily to the heat-induced thermo-mechanical effects rather than molecular unfolding. The current body of evidence supports the notion that the supramolecular collagen structure suffered degradation of various degrees, which gave rise to the observed zonal character of the laser-treated lesion

Validity and reliability of subjective methods to assess sedentary behaviour in adults: a systematic review and meta-analysis.

BACKGROUND: Subjective measures of sedentary behaviour (SB) (i.e. questionnaires and diaries/logs) are widely implemented, and can be useful for capturing type and context of SBs. However, little is known about comparative validity and reliability. The aim of this systematic review and meta-analysis was to: 1) identify subjective methods to assess overall, domain- and behaviour-specific SB, and 2) examine the validity and reliability of these methods. METHODS: The databases MEDLINE, EMBASE and SPORTDiscus were searched up to March 2020. Inclusion criteria were: 1) assessment of SB, 2) evaluation of subjective measurement tools, 3) being performed in healthy adults, 4) manuscript written in English, and 5) paper was peer-reviewed. Data of validity and/or reliability measurements was extracted from included studies and a meta-analysis using random effects was performed to assess the pooled correlation coefficients of the validity. RESULTS: The systematic search resulted in 2423 hits. After excluding duplicates and screening on title and abstract, 82 studies were included with 75 self-reported measurement tools. There was wide variability in the measurement properties and quality of the studies. The criterion validity varied between poor-to-excellent (correlation coefficient [R] range - 0.01- 0.90) with logs/diaries (R = 0.63 [95%CI 0.48-0.78]) showing higher criterion validity compared to questionnaires (R = 0.35 [95%CI 0.32-0.39]). Furthermore, correlation coefficients of single- and multiple-item questionnaires were comparable (1-item R = 0.34; 2-to-9-items R = 0.35; ≥10-items R = 0.37). The reliability of SB measures was moderate-to-good, with the quality of these studies being mostly fair-to-good. CONCLUSION: Logs and diaries are recommended to validly and reliably assess self-reported SB. However, due to time and resources constraints, 1-item questionnaires may be preferred to subjectively assess SB in large-scale observations when showing similar validity and reliability compared to longer questionnaires. REGISTRATION NUMBER: CRD42018105994