Impact of iodized table salt on the sensory characteristics of bread, sausage and pickle

Abstract The impact of iodized table salt on the sensory quality of wheat bread, bologna sausage and pickled cucumber was studied. Table salt (NaCl) content of the products was 1.7, 1.2 and 1.7 g/100 g, respectively. Iodine, added as potassium iodide (KI), was incorporated at levels 0, 25, 50 and 100 mg per kg table salt. Odor, flavor, appearance, and texture were evaluated using deviation from reference descriptive analysis (12 panelists, 4 replicates). Each sample was rated against the non-iodized reference sample (0 mg iodine). The retention of iodine during processing and storage was determined chemically. The iodine level 25 mg/kg, corresponding to current recommendations, did not cause sensory changes in tested products. In sausage, 50 and 100 mg/kg levels were associated with minor changes in texture and color. The maximum retention of iodine was 83% for bread, 98% for sausage, and 51% for cucumber. We did not find any sensory obstacle to using iodized table salt in industrial food production. Due to loss in manufacturing and inadequate intakes, iodine additions higher than currently recommended should be considered.Peer reviewe

The evolutionarily conserved long non‐coding RNA <i>LINC00261</i> drives neuroendocrine prostate cancer proliferation and metastasis <i>via</i> distinct nuclear and cytoplasmic mechanisms

Metastatic neuroendocrine prostate cancer (NEPC) is a highly aggressive disease, whose incidence is rising. Long noncoding RNAs (lncRNAs) represent a large family of disease- and tissue-specific transcripts, most of which are still functionally uncharacterized. Thus, we set out to identify the highly conserved lncRNAs that play a central role in NEPC pathogenesis. To this end, we performed transcriptomic analyses of donor-matched patient-derived xenograft models (PDXs) with immunohistologic features of prostate adenocarcinoma (AR+/PSA+) or NEPC (AR-/SYN+/CHGA+ ) and through differential expression analyses identified lncRNAs that were upregulated upon neuroendocrine transdifferentiation. These genes were prioritized for functional assessment based on the level of conservation in vertebrates. Here, LINC00261 emerged as the top gene with over 3229-fold upregulation in NEPC. Consistently, LINC00261 expression was significantly upregulated in NEPC specimens in multiple patient cohorts. Knockdown of LINC00261 in PC-3 cells dramatically attenuated its proliferative and metastatic abilities, which are explained by parallel downregulation of CBX2 and FOXA2 through distinct molecular mechanisms. In the cell cytoplasm, LINC00261 binds to and sequesters miR-8485 from targeting the CBX2 mRNA, while inside the nucleus, LINC00261 functions as a transcriptional scaffold to induce SMAD-driven expression of the FOXA2 gene. For the first time, these results demonstrate hyperactivation of the LINC00261-CBX2-FOXA2 axes in NEPC to drive proliferation and metastasis, and that LINC00261 may be utilized as a therapeutic target and a biomarker for this incurable disease

HORAS5 promotes cabazitaxel resistance in castration resistant prostate cancer via a BCL2A1-dependent survival mechanism

Background: Long non-coding RNAs (lncRNAs) have been recently identified as key players in several cancer-associated pathways such as metastasis and drug resistance. Emerging evidence indicates that the HORAS5 lncRNA (i.e. linc00161) modulates drug response in different malignancies. In a recently published study, we have shown that HORAS5 promotes the survival of androgen receptor-positive (AR+) castration resistant prostate cancer (CRPC) cells. Preliminary data obtained in our lab show that HORAS5 is involved in response to cabazitaxel, in both AR+ and AR- CRPC cells.Methods: HORAS5 expression was modulated in AR+ and AR- CRPC cells with lentiviral-mediated overexpression and siRNA-based silencing. We measured cell count (Trypan Blue exclusion test) and apoptosis (caspase 3/7) of CRPC cells exposed to clinically achievable concentrations of cabazitaxel. RNA sequencing, RT-qPCR and western blot were used to identify genes regulated by HORAS5 in cabazitaxel-treated cells. We also transfected the cells with antisense oligonucleotides (ASOs), a technology that is currently being tested in clinical trials.Results: Our results show that HORAS5 overexpression increases cabazitaxel IC50 (p = 0.01), while HORAS5 silencing has an opposite effect (p = 0.003). HORAS5 also inhibits caspase activity upon cabazitaxel treatment (p 50 (p = 0.03) in response to cabazitaxel.Conclusions: Our findings show that HORAS5 mediates cabazitaxel resistance in both AR+ and AR- CRPC cells via regulation of the anti-apoptotic BCL2A1. Experiments with ASOs demonstrate the translational potential of HORAS5 inhibition. We are currently assessing HORAS5 expression in biological fluids from patients exposed (or not) to cabazitaxel.Legal entity responsible for the study: Francesco Crea.Funding: The Open University.Disclosure: All authors have declared no conflicts of interest

Dynamics and ligand-induced conformational changes in human prolyl oligopeptidase analyzed by hydrogen/deuterium exchange mass spectrometry

Abstract: Prolyl oligopeptidase (PREP) is conserved in many organisms across life. It is involved in numerous processes including brain function and neuropathology, that require more than its strict proteolytic role. It consists of a seven-bladed beta-propeller juxtaposed to a catalytic alpha/beta-hydrolase domain. The conformational dynamics of PREP involved in domain motions and the gating mechanism that allows substrate accessibility remain elusive. Here we used Hydrogen Deuterium eXchange Mass Spectrometry (HDX-MS) to derive the first near-residue resolution analysis of global PREP dynamics in the presence or absence of inhibitor bound in the active site. Clear roles are revealed for parts that would be critical for the activation mechanism. In the free state, the inter-domain interface is loose, providing access to the catalytic site. Inhibitor binding "locks" the two domains together exploiting prominent interactions between the loop of the first beta-propeller blade and its proximal helix from the alpha/beta-hydrolase domain. Loop A, thought to drive gating, is partially stabilized but remains flexible and dynamic. These findings provide a conformational guide for further dissection of the gating mechanism of PREP, that would impact drug development. Moreover, they offer a structural framework against which to study proteolysis-independent interactions with disordered proteins like alpha-synuclein involved in neurodegenerative disease