Plant biodiversity of mountain grasslands as influenced by dairy farm management in the Eastern Alps

It has been widely demonstrated that farm management affects the plant species composition of grassland. The present study aimed to investigate the effect of farm management on plant species richness and composition in forty-nine small-scale farms breeding dairy cattle, located in the Eastern Italian Alps at two levels of precision: plot and farm levels. Data on housing system, quality scheme, farm productivity, income from milk yield and livestock density were collected through interviews with farmers. In each farm, botanical surveys were carried out in different plots representing the botanical composition of the farmland vegetation. Elevation, slope, type of use, number of hay cuts and type of fertilisation were also recorded. The botanical surveys of the plots on each farm were analysed to describe plant composition at the plot level, then merged to describe plant composition at the farm level. At both levels, grassland botanical composition was found to be affected by farm management. At the plot level, meadows cut 2 and 3 times per year did not exhibit any differences in plant richness, but they differed in plant species, botanical family and phytosociological class composition, with a general simplification of botanical composition. We found fewer phytosociological classes but not fewer plant species or botanical families in plots fertilised with slurry than in plots fertilised with manure or not fertilised, and a change in the botanical composition due to changes in the relative abundance of plant species. At the farm level, we observed a decrease in the number of plant species and phytosociological classes, and changes in plant composition, with increasing milk yield and livestock density. Changes in botanical composition were less evident at the farm level than at the plot level. However, protecting farms and their economic viability is a means of maintaining biodiversity at the plot level

Polyethylene glycol (PEG)-dendron phospholipids as innovative constructs for the preparation of super stealth liposomes for anticancer therapy.

Pegylation of nanoparticles has been widely implemented in the field of drug delivery to prevent macrophage clearance and increase drug accumulation at a target site. However, the shielding effect of polyethylene glycol (PEG) is usually incomplete and transient, due to loss of nanoparticle integrity upon systemic injection. Here, we have synthesized unique PEG-dendron-phospholipid constructs that form super stealth liposomes (SSLs). A \u3b2-glutamic acid dendron anchor was used to attach a PEG chain to several distearoyl phosphoethanolamine lipids, thereby differing from conventional stealth liposomes where a PEG chain is attached to a single phospholipid. This composition was shown to increase liposomal stability, prolong the circulation half-life, improve the biodistribution profile and enhance the anticancer potency of a drug payload (doxorubicin hydrochloride)

Safety of Biologic-DMARDs in Rheumatic Musculoskeletal Disorders: A Population-Based Study over the First Two Waves of COVID-19 Outbreak

This study aims to explore disease patterns of coronavirus disease (COVID-19) in patients with rheumatic musculoskeletal disorders (RMD) treated with immunosuppressive drugs in comparison with the general population. The observational study considered a cohort of RMD patients treated with biologic drugs or small molecules from September 2019 to November 2020 in the province of Udine, Italy. Data include the assessment of both pandemic waves until the start of the vaccination, between February 2020 and April 2020 (first), and between September 2020 and November 2020 (second). COVID-19 prevalence in 1051 patients was 3.5% without significant differences compared to the general population, and the course of infection was generally benign with 2.6% mortality. A small percentage of COVID-19 positive subjects were treated with low doses of steroids (8%). The most used treatments were represented by anti-TNF agents (65%) and anti-IL17/23 agents (16%). More than two-thirds of patients reported fever, while gastro-intestinal symptoms were recorded in 27% of patients and this clinical involvement was associated with longer swab positivity. The prevalence of COVID-19 in RMD patients has been confirmed as low in both waves. The benign course of COVID-19 in our patients may be linked to the very low number of chronic corticosteroids used and the possible protective effect of anti-TNF agents, which were the main class of biologics herein employed. Gastro-intestinal symptoms might be a predictor of viral persistence in immunosup-pressed patients. This finding could be useful to identify earlier COVID-19 carriers with uncommon symptoms, eventually eligible for antiviral drugs

Hyaluronan is a natural and effective immunological adjuvant for protein-based vaccines

One of the main goals of vaccine research is the development of adjuvants that can enhance immune responses and are both safe and biocompatible. We explored the application of the natural polymer hyaluronan (HA) as a promising immunological adjuvant for protein-based vaccines. Chemical conjugation of HA to antigens strongly increased their immunogenicity, reduced booster requirements, and allowed antigen dose sparing. HA-based bioconjugates stimulated robust and long-lasting humoral responses without the addition of other immunostimulatory compounds and proved highly efficient when compared to other adjuvants. Due to its intrinsic biocompatibility, HA allowed the exploitation of different injection routes and did not induce inflammation at the inoculation site. This polymer promoted rapid translocation of the antigen to draining lymph nodes, thus facilitating encounters with antigen-presenting cells. Overall, HA can be regarded as an effective and biocompatible adjuvant to be exploited for the design of a wide variety of vaccines

MicroRNA-133 Controls Brown Adipose Determination in Skeletal Muscle Satellite Cells by Targeting Prdm16

SummaryBrown adipose tissue (BAT) is an energy-dispensing thermogenic tissue that plays an important role in balancing energy metabolism. Lineage-tracing experiments indicate that brown adipocytes are derived from myogenic progenitors during embryonic development. However, adult skeletal muscle stem cells (satellite cells) have long been considered uniformly determined toward the myogenic lineage. Here, we report that adult satellite cells give rise to brown adipocytes and that microRNA-133 regulates the choice between myogenic and brown adipose determination by targeting the 3′UTR of Prdm16. Antagonism of microRNA-133 during muscle regeneration increases uncoupled respiration, glucose uptake, and thermogenesis in local treated muscle and augments whole-body energy expenditure, improves glucose tolerance, and impedes the development of diet-induced obesity. Finally, we demonstrate that miR-133 levels are downregulated in mice exposed to cold, resulting in de novo generation of satellite cell-derived brown adipocytes. Therefore, microRNA-133 represents an important therapeutic target for the treatment of obesity

In situ conjugation of dithiophenol maleimide polymers and oxytocin for stable and reversible polymer–peptide conjugates

The in situ one-pot synthesis of peptide–polymer bioconjugates is reported. Conjugation occurs efficiently without the need for purification of dithiophenol maleimide functionalized polymer as a disulfide bridging agent for the therapeutic oxytocin. Conjugation of polymers was demonstrated to be reversible and to significantly improve the solution stability of oxytocin

Poly(amidoamine)-BSA conjugates synthesised by Michael addition reaction retained enzymatic activity

Polymer-protein conjugates are key to overcome some of the therapeutic protein limitations, including inefficient intracellular delivery. Poly(amidoamine)s are bioresponsive polyelectrolytes, which can form complexes with proteins and promote their delivery into the cytosol of cells. To investigate if conjugation would affect the activity of the protein, two poly(amidoamine)-BSA conjugates were synthesised using a “grafted to” method and Michael addition reaction. Following purification, the conjugates were characterised by electrophoresis, size exclusion chromatography (Mn(C1) = 140.7 kDa ; Mn(C2) = 218.6 kDa) and light scattering (Dh(C1) = 37.5 nm ; Dh(C2) = 75.1 nm). As a result of the conjugation with the cationic polymer, the conjugates had a positive zeta potential (?(C1) = +15.4 mV; ?(C2) = +20.2 mV). TNBS assays demonstrated that 16% to 25% of the protein amine groups were modified and HPLC analysis indicated that the amount of protein in the conjugate was 0.76 mg of BSA/mg of PAA (C1) and 0.43 mg of BSA /mg of PAA (C2). Enzymatic assays indicated the conjugates displayed an esterase activity similar (C1) or reduced ~ 35% (C2) compare to BSA. Altogether the results demonstrated that the conjugation of poly(amidoamine)s to a model protein can lead to the formation of bioconjugates that retain the enzymatic activity of the native protein. Such conjugates could have some application in protein delivery and enzyme engineering for biocatalysis and biosensors

Site-selective protein-modification chemistry for basic biology and drug development.

Nature has produced intricate machinery to covalently diversify the structure of proteins after their synthesis in the ribosome. In an attempt to mimic nature, chemists have developed a large set of reactions that enable post-expression modification of proteins at pre-determined sites. These reactions are now used to selectively install particular modifications on proteins for many biological and therapeutic applications. For example, they provide an opportunity to install post-translational modifications on proteins to determine their exact biological roles. Labelling of proteins in live cells with fluorescent dyes allows protein uptake and intracellular trafficking to be tracked and also enables physiological parameters to be measured optically. Through the conjugation of potent cytotoxicants to antibodies, novel anti-cancer drugs with improved efficacy and reduced side effects may be obtained. In this Perspective, we highlight the most exciting current and future applications of chemical site-selective protein modification and consider which hurdles still need to be overcome for more widespread use.We thank FCT Portugal (FCT Investigator to G.J.L.B.), the EU (Marie-Curie CIG to G.J.L.B. and Marie-Curie IEF to O.B.) and the EPSRC for funding. G.J.L.B. is a Royal Society University Research Fellow.This is the author accepted manuscript. The final version is available from NPG via http://dx.doi.org/10.1038/nchem.239