Cabergoline treatment at dry-off accelerated mammary involution as indicated by mammary secretion composition changes in dairy cows

In ruminants, the early phase of drying-off is a period of mammary gland involution that is marked by the cessation of prolactin (PRL) release. The speed at which the bovine mammary gland involutes following the abrupt cessation of lactation is directly related to the risk of new intramammary infections.ObjectivesOur aim was to assess the effect of PRL inhibition by cabergoline on the speed of the mammary gland involution, through analysis of the changes of mammary secretion composition.Materials and methodsFourteen Holstein dairy cows were injected with a single i.m. administration of 5.6 mg cabergoline (n=7) (Velactis ®, Ceva Sante Animale) or placebo (n=7) at the first day of dryingoff (D0). Mammary secretion samples were collected using a teat-cannula once during lactation (D-6) and at D1, D2, D3, D4, D8 and D14 after the drying-off. The mammary secretion samples were used for milk fat, lactose, true protein, alpha-lactalbumin and SCC analysis. Mammary biopsy samples were collected one week before drying-off (D-6), at D1 and at D8 and used for RNA extraction and RT-PCR analyses.ResultsAs expected, SCC progressively increased whereas lactose content decreased in mammary secretions after drying-off (P < 0.001). The increase in SCC was 2.4 fold higher in cabergoline treated cows than in control cows (P < 0.01). The decrease of lactose content in mammary secretions progressively decreased during involution and was associated with paralleled change in GLUT-1 mRNA level coding the main glucose transporter in the udder. These decreases were faster in cabergoline treated cows compared to controls with lower lactose content in cabergoline treated cows already by D1 than in controls (P < 0.05) and significant decrease in GLUT-1 mRNA levels at D1 and D8 respectively for cabergoline and control treatments compared to D-6 (P ≤ 0.05). Cabergoline treatment tended to increase fat content at D3 after drying-off (P < 0.10). No significant effects of cabergoline treatment were observed both in true protein and in alpha-lactalbumin contents in mammary secretions or in alphalactalbumin and kappa-casein mRNA levels in mammary tissues.ConclusionsThe changes in lactose, SCC and fat in mammary secretions and GLUT-1 mRNA level in the udder, indicate that cabergoline treatment was efficient to hasten the mammary gland involution without affecting milk protein synthesis in the mammary tissue. Cabergoline could facilitate dairy management at the time of dry-off

Carbon-encapsulated iron nanoparticles as reusable adsorbents for micropollutants removal from water

Adsorption represents the most plausible technology for micropollutants removal from water nowadays. Nevertheless, the regeneration of the saturated carbon materials is still an important challenge, being these solids in practice commonly disposed. This work aims at overcoming this issue by using innovative carbonencapsulated iron nanoparticles (CE-nFe). This material was synthesized by a low-cost and green method viz. hydrothermal carbonization (HTC), using olive mill wastewater as carbonaceous source. The solid was fully characterized by different techniques (magnetic properties, elemental analyses, N2-sorption isotherms, pHPZC, ICP, XRD and TEM). It showed a clear core-shell structure of around 40 nm in diameter. The core was mainly formed by zero-valent iron and the shell by graphitized carbon. Accordingly, it showed an essentially mesoporous structure, with a specific surface area of 169 m2 g−1 , and a clear hydrophobic character (pHPZC = 10). Its adsorption performance was investigated using three relevant micropollutants (diclofenac (DCF), sulfamethoxazole (SMX) and metronidazole (MNZ)). A very fast removal of the micropollutants was achieved (30 min at the most, with rate constants in the range of 0.11–0.41 g mg−1 min−1 ). The adsorption isotherms revealed the vertical packing of the adsorbate molecules onto the adsorbent active centers, being the data successfully described by the GAB model. The saturated adsorbents were effectively regenerated by heterogeneous Fenton oxidation, taking advantage of the iron core of CE-nFe and the opened mesoporous carbon shell. The regeneration efficiency increased with increasing the operating temperature (25–75 ◦C) and contact time (1–4 h), as well as the H2O2 dose up to 6 g L-1. The micropollutant nature affected the adsorbent regeneration yield in the order: SMX > DCF > MNZ, consistent with their reactivity towards Fenton oxidationThis research has been supported by the Spanish MINECO through the project CTM-2016-76454-R and by the CM through the project P2018/EMT-4341. M. Munoz and J. Nieto-Sandoval thank the Spanish MINECO for the Ramón y Cajal postdoctoral contract (RYC-2016-20648) and the FPI predoctoral grant (BES-2017-081346), respectivel

Vaccine-associated enhanced disease : case definition and guidelines for data collection, analysis, and presentation of immunization safety data

This is a Brighton Collaboration Case Definition of the term & ldquo;Vaccine Associated Enhanced Disease & rdquo; to be utilized in the evaluation of adverse events following immunization. The Case Definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of vaccines for SARS-CoV-2 vaccines and other emerging pathogens. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected Expert Reviewers prior to submission. (c) 2021 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)

Structural Analysis of the Sulfotransferase (3- O -Sulfotransferase Isoform 3) Involved in the Biosynthesis of an Entry Receptor for Herpes Simplex Virus 1

Heparan sulfate (HS) plays essential roles in assisting herpes simplex virus infection and other biological processes. The biosynthesis of HS includes numerous specialized sulfotransferases that generate a variety of sulfated saccharide sequences, conferring the selectivity of biological functions of HS. We report a structural study of human HS 3-O-sulfotransferase isoform 3 (3-OST-3), a key sulfotransferase that transfers a sulfuryl group to a specific glucosamine in HS generating an entry receptor for herpes simplex virus 1. We have obtained the crystal structure of 3-OST-3 at 1.95 Å in a ternary complex with 3′-phosphoadenosine 5′-phosphate and a tetrasaccharide substrate. Mutational analyses were also performed on the residues involved in the binding of the substrate. Residues Gln255 and Lys368 are essential for the sulfotransferase activity and lie within hydrogen bonding distances to the carboxyl and sulfo groups of the uronic acid unit. These residues participate in the substrate recognition of 3-OST-3. This structure provides atomic level evidence for delineating the substrate recognition and catalytic mechanism for 3-OST-3

Phenological Study of 53 Spanish Minority Grape Varieties to Search for Adaptation of Vitiviniculture to Climate Change Conditions

The main phenological stages (budburst, flowering, veraison, and ripeness) of 53 Spanish minority varieties were studied to determine their potential to help winegrowers adapt to climate change conditions. In total, 43 varieties were studied in the same location in Spain (Alcalá de Henares, in the Madrid region) and 10 varieties in 5 other regions (Galicia, Navarre, Catalonia, Extremadura, and Andalusia). Other traits of agronomic and oenological interest, such as yield and acidity, were also monitored. The results allow for the grouping of the varieties into several clusters according to the time of ripeness (very early—only for red varieties—and early, intermediate, and late, for both red and white varieties) and yield (high, medium, and low). The total acidity in the grape juice ranged from 3 to 11 g of tartaric acid/L. The average temperatures were higher (up to 3–4 °C during summer) compared to historical averages during the 1957–2021 time period. Advanced phenology phases and reduced acidity are regarded as negative effects of climate change for winegrowing practices. Since some minority varieties showed late or intermediate ripening, high acidity, and high (1 Kg/shoot) or medium (0.5 Kg/shoot) yield, our findings suggest that they may be cultivated in the coming years by winegrowers as an approach to mitigate climate change effects.info:eu-repo/semantics/publishedVersio

MYC activation impairs cell-intrinsic IFNγ signaling and confers resistance to anti-PD1/PD-L1 therapy in lung cancer

Elucidating the adaptive mechanisms that prevent host immune response in cancer will help predict efficacy of anti-programmed death-1 (PD1)/L1 therapies. Here, we study the cell-intrinsic response of lung cancer (LC) to interferon-y (IFNy), a cytokine that promotes immunoresponse and modulates programmed death-ligand 1 (PD-L1) levels. We report complete refractoriness to IFNy in a subset of LCs as a result of JAK2 or IFNGR1 inactivation. A submaximal response affects another subset that shows constitutive low levels of IFNy-stimulated genes (IySGs) coupled with decreased H3K27ac (histone 3 acetylation at lysine 27) depo-sition and promoter hypermethylation and reduced IFN regulatory factor 1 (IRF1) recruitment to the DNA on IFNy stimulation. Most of these are neuroendocrine small cell LCs (SCLCs) with oncogenic MYC/MYCL1/ MYCN. The oncogenic activation of MYC in SCLC cells downregulates JAK2 and impairs IySGs stimulation by IFNy. MYC amplification tends to associate with a worse response to anti-PD1/L1 therapies. Hence alterations affecting the JAK/STAT pathway and MYC activation prevent stimulation by IFNy and may predict anti-PD1/L1 efficacy in LC

Brain-muscle communication prevents muscle aging by maintaining daily physiology

Muñoz-Cánoves, Pur

Elevated frequencies of leukemic myeloid and plasmacytoid dendritic cells in acute myeloid leukemia with the FLT3 internal tandem duplication

Some 30% of acute myeloid leukemia (AML) patients display an internal tandem duplication (ITD) mutation in the FMS-like tyrosine kinase 3 (FLT3) gene. FLT3-ITDs are known to drive hematopoietic stem cells towards FLT3 ligand independent growth, but the effects on dendritic cell (DC) differentiation during leukemogenesis are not clear. We compared the frequency of cells with immunophenotype of myeloid DC (mDC: Lin−, HLA-DR+, CD11c+, CD86+) and plasmacytoid DC (pDC: Lin−, HLA-DR+, CD123+, CD86+) in diagnostic samples of 47 FLT3-ITD− and 40 FLT3-ITD+ AML patients. The majority of ITD+ AML samples showed high frequencies of mDCs or pDCs, with significantly decreased HLA-DR expression compared with DCs detectable in ITD− AML samples. Interestingly, mDCs and pDCs sorted out from ITD+ AML samples contained the ITD insert revealing their leukemic origin and, upon ex vivo culture with cytokines, they acquired DC morphology. Notably, mDC/pDCs were detectable concurrently with single lineage mDCs and pDCs in all ITD+ AML (n = 11) and ITD− AML (n = 12) samples analyzed for mixed lineage DCs (Lin−, HLA-DR+, CD11c+, CD123+). ITD+ AML mDCs/pDCs could be only partially activated with CD40L and CpG for production of IFN-α, TNF-α, and IL-1α, which may affect the anti-leukemia immune surveillance in the course of disease progression

Human Papillomavirus Genotype Distribution in Czech Women and Men with Diseases Etiologically Linked to HPV

The HPV prevalence and genotype distribution are important for the estimation of the impact of HPV-based cervical cancer screening and HPV vaccination on the incidence of diseases etiologically linked to HPVs. The HPV genotype distribution varies across different geographical regions. Therefore, we investigated the type-specific HPV prevalence in Czech women and men with anogenital diseases.We analyzed 157 squamous cell carcinoma samples, 695 precancerous lesion samples and 64 cervical, vulvar and anal condylomata acuminate samples. HPV detection and typing were performed by PCR with GP5+/6+ primers, reverse line blot assay and sequencing. samples. HPV types 6 and/or 11 were detected in 84% samples of condylomata acuminate samples.The prevalence of vaccinal and related HPV types in patients with HPV-associated diseases in the Czech Republic is very high. We may assume that the implementation of routine vaccination against HPV would greatly reduce the burden of HPV-associated diseases in the Czech Republic

Interleukin-6 gene (IL-6): a possible role in brain morphology in the healthy adult brain

Background: Cytokines such as interleukin 6 (IL-6) have been implicated in dual functions in neuropsychiatric disorders. Little is known about the genetic predisposition to neurodegenerative and neuroproliferative properties of cytokine genes. In this study the potential dual role of several IL-6 polymorphisms in brain morphology is investigated. Methodology: In a large sample of healthy individuals (N = 303), associations between genetic variants of IL-6 (rs1800795; rs1800796, rs2069833, rs2069840) and brain volume (gray matter volume) were analyzed using voxel-based morphometry (VBM). Selection of single nucleotide polymorphisms (SNPs) followed a tagging SNP approach (e.g., Stampa algorigthm), yielding a capture 97.08% of the variation in the IL-6 gene using four tagging SNPs. Principal findings/results: In a whole-brain analysis, the polymorphism rs1800795 (−174 C/G) showed a strong main effect of genotype (43 CC vs. 150 CG vs. 100 GG; x = 24, y = −10, z = −15; F(2,286) = 8.54, puncorrected = 0.0002; pAlphaSim-corrected = 0.002; cluster size k = 577) within the right hippocampus head. Homozygous carriers of the G-allele had significantly larger hippocampus gray matter volumes compared to heterozygous subjects. None of the other investigated SNPs showed a significant association with grey matter volume in whole-brain analyses. Conclusions/significance: These findings suggest a possible neuroprotective role of the G-allele of the SNP rs1800795 on hippocampal volumes. Studies on the role of this SNP in psychiatric populations and especially in those with an affected hippocampus (e.g., by maltreatment, stress) are warranted.Bernhard T Baune, Carsten Konrad, Dominik Grotegerd, Thomas Suslow, Eva Birosova, Patricia Ohrmann, Jochen Bauer, Volker Arolt, Walter Heindel, Katharina Domschke, Sonja Schöning, Astrid V Rauch, Christina Uhlmann, Harald Kugel and Udo Dannlowsk