Targeted phenolic profile of radler beers by HPLC-ESI-MS/MS: the added value of hesperidin to beer antioxidants

The well-known health beneficial properties of beer are mainly due to phenolic antioxidants. Citrus-flavored beers represent a growing side-market in the beer industry, sparingly investigated to date. The phenolic profile of commercial radler beers (R1, R2) was investigated to evaluate the impact of the lemon juice added to beer in the industrial production. Results were compared to those obtained for opportunely chosen commercial beer (B) and lemonade (L). The study was carried out by an HPLC-MS/MS with an electrospray ionization source in selected ion recording mode, analyzing in a single chromatographic run 26 compounds belonging to the different phenolic classes of hydroxybenzoic, hydroxycinnamic and caffeoylquinic acids, flavonoids and prenylflavonoids. Different phenolic profiles were found for R1 and R2, mainly ascribed to different malt/hop/recipe used for the beer. High to very high level of hesperidin were found in the radlers, so that a major impact on phenolic antioxidants of the radlers was due to the lemon. Similarly, a major impact of the lemon aromas was found, D-limonene being the dominant peak resulting from the GC-MS analysis of the volatile fraction of the radlers. Graphical Abstract: [Figure not available: see fulltext.]

MAD2L2 promotes open chromatin in embryonic stem cells and derepresses the Dppa3 locus.

The chromatin of naive embryonic stem cells (ESCs) has a largely open configuration, as evident by the lack of condensed heterochromatin and the hypomethylation of DNA. Several molecular mechanisms promoting this constellation were previously identified. Here we present evidence for an important epigenetic function of MAD2L2, a protein originally known for its role in DNA damage repair, and for its requirement in germ cell development. We demonstrate using super-resolution microscopy that numerous MAD2L2 microfoci are exclusively associated with euchromatin, similar to other factors of the DNA damage response. In the absence of MAD2L2 the amount of heterochromatin demarcated by H3K9me2 was significantly increased. Among the most strongly suppressed genes was Dppa3, an ESC- and germ-cell-specific gene regulating DNA methylation. In Mad2l2-deficient ESCs 5-methylcytosine levels were globally increased, while several imprinted genes became hypomethylated and transcriptionally activated. Our results emphasize the important function of MAD2L2 for the open chromatin configuration of ESCs

Macrophage Activation in Follicular Conjunctivitis during the COVID-19 Pandemic

Among the symptoms of SARS-CoV-2, follicular conjunctivitis has become relevant. The conjunctiva acts as an open lymph node, reacting to the viral antigen that binds the epithelial cells, forming follicles of B cells with activated T cells and NK cells on its surface, which, in turn, talk to monocyte-derived inflammatory infected macrophages. Here, the NLRP3 inflammasome is a major driver in releasing pro-inflammatory factors such as IL-6 and caspase-1, leading to follicular conjunctivitis and bulbar congestion, even as isolated signs in the ‘asymptomatic’ patient

Tumor promoter phorbol myristate acetate inhibits Ca2+ influx through voltage-gated Ca2+ channels in two secretory cell lines, PC12 and RINm5F.

Protein kinase C is known to be involved both in initiation and termination of cellular responses due to phosphoinositide breakdown. Here we report that in PC12 cells (a line of neurosecretory cells derived from a rat pheochromocytoma), pretreatment with nanomolar concentrations of phorbol myristate acetate, PMA, which is believed to specifically activate protein kinase C, inhibits the cytosolic-free Ca2+ concentration rise induced by depolarizing agents. In contrast, plasma membrane potential and 45Ca efflux from preloaded cells were unaffected by PMA pretreatment. Inhibition by PMA and diacylglycerol of the cytosolic-free Ca2+ concentration rise induced by depolarization was observed also in another cell line, the insulin secreting line RINm5F. These results raise the possibility that the voltage-gated Ca2+ channel is under inhibitory control by protein kinase C

Charting a DNA repair roadmap for immunoglobulin class switch recombination

Immunoglobulin (Ig) class switch recombination (CSR) is the process occurring in mature B cells that diversifies the effector component of antibody responses. CSR is initiated by the activity of the B cell-specific enzyme activation-induced cytidine deaminase (AID), which leads to the formation of programmed DNA double-strand breaks (DSBs) at the Ig heavy chain (Igh) locus. Mature B cells use a multilayered and complex regulatory framework to ensure that AID-induced DNA breaks are channeled into productive repair reactions leading to CSR, and to avoid aberrant repair events causing lymphomagenic chromosomal translocations. Here, we review the DNA repair pathways acting on AID-induced DSBs and their functional interplay, with a particular focus on the latest developments in their molecular composition and mechanistic regulation

DNA repair and antibody diversification: the 53BP1 paradigm

The DNA double-strand break (DSB) repair factor 53BP1 has long been implicated in V(D)J and class switch recombination (CSR) of mammalian lymphocyte receptors. However, the dissection of the underlying molecular activities is hampered by a paucity of studies [V(D)J] and plurality of phenotypes (CSR) associated with 53BP1 deficiency. Here, we revisit the currently accepted roles of 53BP1 in antibody diversification in view of the recent identification of its downstream effectors in DSB protection and latest advances in genome architecture. We propose that, in addition to end protection, 53BP1-mediated end-tethering stabilization is essential for CSR. Furthermore, we support a pre-DSB role during V(D)J recombination. Our perspective underscores the importance of evaluating repair of DSBs in relation to their dynamic architectural contexts