Gastroethnobotany of Halophytes

The halophytes are a specialized group of plants among which there are some representatives that have been cultivated for millenia. Domesticated or wild lineages are also consumed as food, being chard and dates fruits a good example of it. Other species highly appreciated and consumed locally are collected from wild, like Crithmum, and form part of the traditional cuisine of various areas of the planet. Within this group, some are the object of global cultivation and are distributed by haute cuisine networks such as Salicornia, Mertensia, or Tetragonia. Finally, there are other wild halophytes that were only consumed in situations of extreme need such as famines. Generally, they have not been appreciated by the populations that collect them, such as Halosarcia, Suaeda, or Arthrocnemum. The case of Tetragonia, a species native to Australia, is very significant. The perception of the aborigines, who did not eat it, was different from that of the European settlers who did consume them and even sent their seeds to Europe for domestication and cultivation as new vegetable. Currently, the new gastronomy, sometimes based on tradition and others on experimentation itself, has incorporated into the kitchen many news halophytes and with them has developed numerous unpublished and novel recipes

Remodeling of the m6A RNA landscape in the conversion of acute lymphoblastic leukemia cells to macrophages

We thank CERCA Programme/Generalitat de Catalunya for institutional support. This work was supported by the Health Department PERIS-project no. SLT/002/16/00374 and AGAUR-projects no. 2017SGR1080 of the Catalan Government (Generalitat de Catalunya); Ministerio de Ciencia e Innovación (MCI), Agencia Estatal de Investigación (AEI) and European Regional Development Fund (ERDF) project no. RTI2018-094049-B-I00; the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant agreement No. 743168); the Varda and Boaz Dotan Research Center in Hemato-oncology affiliated to the Tel Aviv University; the Cellex Foundation; and “la Caixa” Banking Foundation (LCF/PR/GN18/51140001). ME is an ICREA Research Professor.Peer Reviewed"Article signat per 12 autors/es: Alberto Bueno-Costa, David Piñeyro, Carlos A. García-Prieto, Vanessa Ortiz-Barahona, Laura Martinez-Verbo, Natalie A. Webster, Byron Andrews, Nitzan Kol, Chen Avrahami, Sharon Moshitch-Moshkovitz, Gideon Rechavi & Manel Esteller"Postprint (published version

Preoperative Exercise during Neoadjuvant Therapy for Pancreatic Cancer: A Pilot Study

Exercise improves cancer treatment outcomes including health-related quality of life and physical functioning. Patients with pancreatic cancer are generally older adults, and frailty and cachexia are prevalent. Chemotherapy and chemoradiation are increasingly administered prior to pancreatic cancer surgery, and sarcopenia has been shown to accompany these therapies. Preoperative exercise may improve health, well-being, and perioperative outcomes among patients undergoing preoperative therapy for pancreatic cancer. The purpose of this pilot study was to determine the feasibility of exercise in this context. Feasibility was defined as patients completing, on average, 60% of recommended weekly exercise minutes. Twenty patients (M=64 years old, SD=9.9; 42% female) enrolled in a home-based exercise program during preoperative therapy (chemotherapy and/or chemoradiation and preoperative “rest”, M=21.2 weeks total, SD=16.4). Exercise recommendations included moderate-intensity walking for 20-30 minutes/day on ≥3 days/week and moderate-intensity resistance exercises for 30-45 minutes/day on ≥2 days/week. Exercise recommendations (120 minutes of moderate-intensity activity/week) were based on American College of Sports Medicine and American Cancer Society recommendations (150 minutes of moderate-intensity activity/week), but reduced due to patients’ older age and concurrent preoperative therapy. Resistance exercises targeted upper body, lower body, and abdominal muscles, and patients were instructed to perform 3 sets of 8-12 repetitions of multiple exercises for each region during each session. Patients received Yamax Digiwalker pedometers, graded resistance tube sets, and booklets and DVDs with instructions and safety tips. Research staff provided detailed instructions and resistance exercise demonstrations at enrollment and monitored and encouraged adherence with biweekly phone calls. Patients recorded minutes of walking and resistance exercise in daily logs. On average, patients reported 73.9 minutes of walking (\u3e100% of recommendation, SD=72.4) and 43.1 minutes of resistance exercise per week (71.8% of recommendation, SD=39.0). Patients reported the most walking during chemoradiation (M=94.7 minutes/week, SD=104.3), followed by preoperative “rest” (M=77.4 minutes/week, SD=80.4), and chemotherapy (M=70.8 minutes/week, SD=75.2). Patients reported the most resistance exercise during the preoperative “rest” period (M=51.6 minutes/week, SD=52.3), followed by chemoradiation (M=38.0 minutes/week, SD=36.8), and chemotherapy (M=31.1 minutes/week, SD=38.1). Walking and resistance exercise are feasible for patients undergoing preoperative therapy for pancreatic cancer. Varying levels of fatigue and treatment-related side effects may affect exercise during different treatment phases

Fucoidan Inhibition of Osteosarcoma Cells Is Species and Molecular Weight Dependent.

Fucoidan is a brown algae-derived polysaccharide having several biomedical applications. This study simultaneously compares the anti-cancer activities of crude fucoidans from Fucus vesiculosus and Sargassum filipendula, and effects of low (LMW, 10-50 kDa), medium (MMW, 50-100 kDa) and high (HMW, >100 kDa) molecular weight fractions of S. filipendula fucoidan against osteosarcoma cells. Glucose, fucose and acid levels were lower and sulphation was higher in F. vesiculosus crude fucoidan compared to S. filipendula crude fucoidan. MMW had the highest levels of sugars, acids and sulphation among molecular weight fractions. There was a dose-dependent drop in focal adhesion formation and proliferation of cells for all fucoidan-types, but F. vesiculosus fucoidan and HMW had the strongest effects. G1-phase arrest was induced by F. vesiculosus fucoidan, MMW and HMW, however F. vesiculosus fucoidan treatment also caused accumulation in the sub-G1-phase. Mitochondrial damage occurred for all fucoidan-types, however F. vesiculosus fucoidan led to mitochondrial fragmentation. Annexin V/PI, TUNEL and cytochrome c staining confirmed stress-induced apoptosis-like cell death for F. vesiculosus fucoidan and features of stress-induced necrosis-like cell death for S. filipendula fucoidans. There was also variation in penetrability of different fucoidans inside the cell. These differences in anti-cancer activity of fucoidans are applicable for osteosarcoma treatment

Systemic insulin sensitivity is regulated by GPS2 inhibition of AKT ubiquitination and activation in adipose tissue

OBJECTIVE: Insulin signaling plays a unique role in the regulation of energy homeostasis and the impairment of insulin action is associated with altered lipid metabolism, obesity, and Type 2 Diabetes. The main aim of this study was to provide further insight into the regulatory mechanisms governing the insulin signaling pathway by investigating the role of non-proteolytic ubiquitination in insulin-mediated activation of AKT. METHODS: The molecular mechanism of AKT regulation through ubiquitination is first dissected in vitro in 3T3-L1 preadipocytes and then validated in vivo using mice with adipo-specific deletion of GPS2, an endogenous inhibitor of Ubc13 activity (GPS2-AKO mice). RESULTS: Our results indicate that K63 ubiquitination is a critical component of AKT activation in the insulin signaling pathway and that counter-regulation of this step is provided by GPS2 preventing AKT ubiquitination through inhibition of Ubc13 enzymatic activity. Removal of this negative checkpoint, through GPS2 downregulation or genetic deletion, results in sustained activation of insulin signaling both in vitro and in vivo. As a result, the balance between lipid accumulation and utilization is shifted toward storage in the adipose tissue and GPS2-AKO mice become obese under normal laboratory chow diet. However, the adipose tissue of GPS2-AKO mice is not inflamed, the levels of circulating adiponectin are elevated, and systemic insulin sensitivity is overall improved. CONCLUSIONS: Our findings characterize a novel layer of regulation of the insulin signaling pathway based on non-proteolytic ubiquitination of AKT and define GPS2 as a previously unrecognized component of the insulin signaling cascade. In accordance with this role, we have shown that GPS2 presence in adipocytes modulates systemic metabolism by restricting the activation of insulin signaling during the fasted state, whereas in absence of GPS2, the adipose tissue is more efficient at lipid storage, and obesity becomes uncoupled from inflammation and insulin resistance

The Origin, Epidemiology, and Phylodynamics of Human Immunodeficiency Virus Type 1 CRF47_BF

CRF47_BF is a circulating recombinant form (CRF) of the human immunodeficiency virus type 1 (HIV-1), the etiological agent of AIDS. CRF47_BF represents one of 19 CRFx_BFs and has a geographic focus in Spain, where it was first identified in 2010. Since its discovery, CRF47_BF has expanded considerably in Spain, predominantly through heterosexual contact (∼56% of the infections). Little is known, however, about the origin and diversity of this CRF or its epidemiological correlates, as very few samples have been available so far. This study conducts a phylogenetic analysis with representatives of all CRFx_BF sequence types along with HIV-1 M Group subtypes to validate that the CRF47_BF sequences share a unique evolutionary history. The CRFx_BF sequences cluster into a single, not well supported, clade that includes their dominant parent subtypes (B and F). This clade also includes subtype D and excludes sub-subtype F2. However, the CRF47_BF sequences all share a most recent common ancestor. Further analysis of this clade couples CRF47_BF protease-reverse transcriptase sequences and epidemiological data from an additional 87 samples collected throughout Spain, as well as additional CRF47_BF database sequences from Brazil and Spain to investigate the origin and phylodynamics of CRF47_BF. The Spanish region with the highest proportion of CRF47_BF samples in the data set was the Basque Country (43.7%) with Navarre next highest at 19.5%. We include in our analysis epidemiological data on host sex, mode of transmission, time of collection, and geographic region. The phylodynamic analysis indicates that CRF47_BF originated in Brazil around 1999-2000 and spread to Spain from Brazil in 2002-2003. The virus spread rapidly throughout Spain with an increase in population size from 2011 to 2015 and leveling off more recently. Three strongly supported clusters associated with Spanish regions (Basque Country, Navarre, and Aragon), together comprising 60.8% of the Spanish samples, were identified, one of which was also associated with transmission among men who have sex with men. The expansion in Spain of CRF47_BF, together with that of other CRFs and subtype variants of South American origin, previously reported, reflects the increasing relationship between the South American and European HIV-1 epidemics.The study was supported by Acción Estratégica en Salud Intramural (AESI) program of Instituto de Salud Carlos III, projects “Estudio sobre Vigilancia Epidemiológica Molecular de la Infección por VIH-1 en España,” PI16CIII/00033, and “Epidemiología Molecular del VIH-1 en España y su Utilidad para Investigaciones Biológicas y en Vacunas,” PI19CIII/00042; Red de Investigación en SIDA (RIS), Instituto de Salud Carlos III, Plan Nacional I+D+I, project RD16ISCIII/0002/0004; and scientific agreements with the Governments of Galicia (MVI 1004/16) and Basque Country (MVI 1001/16).N

Microsatellite primers for two threatened orchids in Florida: Encyclia tampensis and Cyrtopodium punctatum (Orchidaceae)1

Premise of the study: The Million Orchid Project at Fairchild Tropical Botanic Garden is an initiative to propagate native orchids for reintroduction into Miami?s urban landscapes. The aim of this study was to develop microsatellites for Encyclia tampensis and Cyrtopodium punctatum (Orchidaceae). Methods and Results: Ten microsatellites were developed for each species. For E. tampensis sampled from the natural population, allele numbers ranged from one to four, with an average observed heterozygosity (Ho) of 0.314 and average expected heterozygosity (He) of 0.281. For the individuals from cultivation, allele numbers ranged from one to six, with an average Ho of 0.35 and an average He of 0.224. For C. punctatum, allele numbers ranged from one to three, with an average Ho of 0.257 and an average He of 0.272. Conclusions: These microsatellites will be used to assess the genetic diversity of natural and cultivated populations with the intention of guiding genetic breeding under the Million Orchid Project

Insulin Resistance in Women Correlates with Chromatin Histone Lysine Acetylation, Inflammatory Signaling, and Accelerated Aging

BackgroundEpigenetic changes link medical, social, and environmental factors with cardiovascular and kidney disease and, more recently, with cancer. The mechanistic link between metabolic health and epigenetic changes is only starting to be investigated. In our in vitro and in vivo studies, we performed a broad analysis of the link between hyperinsulinemia and chromatin acetylation; our top "hit" was chromatin opening at H3K9ac.MethodsBuilding on our published preclinical studies, here, we performed a detailed analysis of the link between insulin resistance, chromatin acetylation, and inflammation using an initial test set of 28 women and validation sets of 245, 22, and 53 women.ResultsChIP-seq identified chromatin acetylation and opening at the genes coding for TNFα and IL6 in insulin-resistant women. Pathway analysis identified inflammatory response genes, NFκB/TNFα-signaling, reactome cytokine signaling, innate immunity, and senescence. Consistent with this finding, flow cytometry identified increased senescent circulating peripheral T-cells. DNA methylation analysis identified evidence of accelerated aging in insulin-resistant vs. metabolically healthy women.ConclusionsThis study shows that insulin-resistant women have increased chromatin acetylation/opening, inflammation, and, perhaps, accelerated aging. Given the role that inflammation plays in cancer initiation and progression, these studies provide a potential mechanistic link between insulin resistance and cancer

Whole Genome Sequencing of Australian Candida glabrata Isolates Reveals Genetic Diversity and Novel Sequence Types

Candida glabrata is a pathogen with reduced susceptibility to azoles and echinocandins. Analysis by traditional multilocus sequence typing (MLST) has recognized an increasing number of sequence types (STs), which vary with geography. Little is known about STs of C. glabrata in Australia. Here, we utilized whole genome sequencing (WGS) to study the genetic diversity of 51 Australian C. glabrata isolates and sought associations between STs over two time periods (2002–2004, 2010–2017), and with susceptibility to fluconazole by principal component analysis (PCA). Antifungal susceptibility was determined using Sensititre YeastOneTM Y010 methodology and WGS performed on the NextSeq 500 platform (Illumina) with in silico MLST STs inferred by WGS data. Single nucleotide polymorphisms (SNPs) in genes linked to echinocandin, azole and 5-fluorocytosine resistance were analyzed. Of 51 isolates, WGS identified 18 distinct STs including four novel STs (ST123, ST124, ST126, and ST127). Four STs accounted for 49% of isolates (ST3, 15.7%; ST83, 13.7%; ST7, 9.8%; ST26, 9.8%). Split-tree network analysis resolved isolates to terminal branches; many of these comprised multiple isolates from disparate geographic settings but four branches contained Australian isolates only. ST3 isolates were common in Europe, United States and now Australia, whilst ST8 and ST19, relatively frequent in the United States, were rare/absent amongst our isolates. There was no association between ST distribution (genomic similarity) and the two time periods or with fluconazole susceptibility. WGS identified mutations in the FKS1 (S629P) and FKS2 (S663P) genes in three, and one, echinocandin-resistant isolate(s), respectively. Both mutations confer phenotypic drug resistance. Twenty-five percent (13/51) of isolates were fluconazole-resistant (MIC ≥ 64 μg/ml) of which 9 (18%) had non wild-type MICs to voriconazole and posaconazole. Multiple SNPs were present in genes linked to azole resistance such as CgPDR1 and CgCDR1, as well as several in MSH2; however, SNPs occurred in both azole-susceptible and azole-resistant isolates. Although no particular SNP in these genes was definitively associated with resistance, azole-resistant/non-wild type isolates had a propensity to harbor SNPs resulting in amino acid substitutions in Pdr1 beyond the first 250 amino acid positions. The presence of SNPs may be markers of STs. Our study shows the value of WGS for high-resolution sequence typing of C. glabrata, discovery of novel STs and potential to monitor trends in genetic diversity. WGS assessment for echinocandin resistance augments phenotypic susceptibility testing