Flux regulation through glycolysis and respiration is balanced by inositol pyrophosphates in yeast.

Although many prokaryotes have glycolysis alternatives, it's considered as the only energy-generating glucose catabolic pathway in eukaryotes. Here, we managed to create a hybrid-glycolysis yeast. Subsequently, we identified an inositol pyrophosphatase encoded by OCA5 that could regulate glycolysis and respiration by adjusting 5-diphosphoinositol 1,2,3,4,6-pentakisphosphate (5-InsP7) levels. 5-InsP7 levels could regulate the expression of genes involved in glycolysis and respiration, representing a global mechanism that could sense ATP levels and regulate central carbon metabolism. The hybrid-glycolysis yeast did not produce ethanol during growth under excess glucose and could produce 2.68 g/L free fatty acids, which is the highest reported production in shake flask of Saccharomyces cerevisiae. This study demonstrated the significance of hybrid-glycolysis yeast and determined Oca5 as an inositol pyrophosphatase controlling the balance between glycolysis and respiration, which may shed light on the role of inositol pyrophosphates in regulating eukaryotic metabolism.

Reprogramming Yeast Metabolism from Alcoholic Fermentation to Lipogenesis.

Engineering microorganisms for production of fuels and chemicals often requires major re-programming of metabolism to ensure high flux toward the product of interest. This is challenging, as millions of years of evolution have resulted in establishment of tight regulation of metabolism for optimal growth in the organism's natural habitat. Here, we show through metabolic engineering that it is possible to alter the metabolism of Saccharomyces cerevisiae from traditional ethanol fermentation to a pure lipogenesis metabolism, resulting in high-level production of free fatty acids. Through metabolic engineering and process design, we altered subcellular metabolic trafficking, fine-tuned NADPH and ATP supply, and decreased carbon flux to biomass, enabling production of 33.4 g/L extracellular free fatty acids. We further demonstrate that lipogenesis metabolism can replace ethanol fermentation by deletion of pyruvate decarboxylase enzymes followed by adaptive laboratory evolution. Genome sequencing of evolved strains showed that pyruvate kinase mutations were essential for this phenotype.

Perception of maxillary incisor inclination and its correlation with dental cephalometric measurements.

OBJECTIVE: To correlate the clinical perception of maxillary incisor inclination from photographs of the smiling face with cephalometric measurements, using conventional incisor axis reference points and crown reference points. DESIGN: Cross-sectional study. SETTING: Department of Orthodontics, School of Dentistry, University of Lisbon (Portugal). PARTICIPANTS: Eight orthodontists. METHODS: The perception of maxillary incisor inclination of 47 female patients (mean age 23.4 ± 1.5 years) was evaluated by eight orthodontists. The participants' photographs (smiling frontal, smiling three-quarter and smiling profile) were shown to each assessor and a continuous visual analogue rating scale was used to assess the perception of maxillary incisor inclination. Pearson's correlation and linear regression were calculated between each cephalometric measurement and the perception of incisor inclination. RESULTS: Anatomical crown inclination measurements U1ac-FH (r = 0.854; P < 0.01) and U1ac-SN (r = 0.845; P < 0.01) had the highest correlation values with the assessors' perception of maxillary incisor inclination. Conventional incisor axis measurements showed the lowest correlation values (r = 0.668-0.756). CONCLUSION: Cephalometric measurements of the labial surface of the anatomical crown of the maxillary incisors showed the strongest correlations with the clinical perception of maxillary incisor inclination from photographs. For optimal aesthetics, the inclination of the labial surface of maxillary incisor crown should be evaluated.

Elucidating aromatic acid tolerance at low pH in Saccharomyces cerevisiae using adaptive laboratory evolution.

Toxicity from the external presence or internal production of compounds can reduce the growth and viability of microbial cell factories and compromise productivity. Aromatic compounds are generally toxic for microorganisms, which makes their production in microbial hosts challenging. Here we use adaptive laboratory evolution to generate Saccharomyces cerevisiae mutants tolerant to two aromatic acids, coumaric acid and ferulic acid. The evolution experiments were performed at low pH (3.5) to reproduce conditions typical of industrial processes. Mutant strains tolerant to levels of aromatic acids near the solubility limit were then analyzed by whole genome sequencing, which revealed prevalent point mutations in a transcriptional activator (Aro80) that is responsible for regulating the use of aromatic amino acids as the nitrogen source. Among the genes regulated by Aro80, ESBP6 was found to be responsible for increasing tolerance to aromatic acids by exporting them out of the cell. Further examination of the native function of Esbp6 revealed that this transporter can excrete fusel acids (byproducts of aromatic amino acid catabolism) and this role is shared with at least one additional transporter native to S. cerevisiae (Pdr12). Besides conferring tolerance to aromatic acids, ESBP6 overexpression was also shown to significantly improve the secretion in coumaric acid production strains. Overall, we showed that regulating the activity of transporters is a major mechanism to improve tolerance to aromatic acids. These findings can be used to modulate the intracellular concentration of aromatic compounds to optimize the excretion of such products while keeping precursor molecules inside the cell.

Napping behaviour, daytime sleepiness, and arousal in high performance athletes and non-athlete controls.

Napping offers a strategy to manage sleep, aid recovery and enhance performance in elite sport. However, relatively little research attention has focussed on the natural history of athlete napping or tested the widely held assumption that athlete napping is mainly a consequence of degraded night-time sleep. Within a sample of 158 team (n = 76) and individual (n = 80) sport athletes, and 82 non-athlete controls, we analysed napping behaviour in relation to sleep quality, daytime sleepiness, and pre-sleep somatic and cognitive arousal. There was no significant association between athlete/non-athlete status and the prevalence, frequency, or duration of naps. Comparisons of athlete nappers and non-nappers found no significant differences in sleep quantity or quality. While nap propensity was significantly related to higher daytime sleepiness, this influence was moderated or augmented by levels of pre-sleep cognitive arousal. For some nappers, those with higher levels of arousal may need to be sleepier than those with lower levels of arousal in order to successfully initiate daytime sleep. Approximately 50% of athletes did not nap. If the benefits of athlete napping are to be fully exploited, the needs of this substantial group for whom napping may be problematic should be recognised and addressed.

Adapting Elements of Cleft Care Protocols in Low- and Middle-income Countries During and After COVID-19: A Process-driven Review With Recommendations.

A consortium of global cleft professionals, predominantly from low- and middle-income countries, identified adaptations to cleft care protocols during and after COVID-19 as a priority learning area of need.A multidisciplinary international working group met on a videoconferencing platform in a multi-staged process to make consensus recommendations for adaptations to cleft protocols within resource-constrained settings. Feedback was sought from a roundtable discussion forum and global organizations involved in comprehensive cleft care.Foundational principles were agreed to enable recommendations to be globally relevant and two areas of focus within the specified topic were identified. First the safety aspects of cleft surgery protocols were scrutinized and COVID-19 adaptations, specifically in the pre- and perioperative periods, were highlighted. Second, surgical procedures and cleft care services were prioritized according to their relationship to functional outcomes and time-sensitivity. The surgical procedures assigned the highest priority were emergent interventions for breathing and nutritional requirements and primary palatoplasty. The cleft care services assigned the highest priority were new-born assessments, pediatric support for children with syndromes, management of acute dental or auditory infections and speech pathology intervention.A collaborative, interdisciplinary and international working group delivered consensus recommendations to assist with the provision of cleft care in low- and middle-income countries. At a time of global cleft care delays due to COVID-19, a united approach amongst global cleft care providers will be advantageous to advocate for children born with cleft lip and palate in resource-constrained settings.

Laser ablation fabrication of ap-NiO/n-Si heterojunction for broadband and self-powered UV-Visible-NIR photodetection.

We report on the optoelectronic characteristics ofp-NiO/n-Si heterojunction photodiode for broadband photodetection, fabricated by depositing ap-type NiO thin film onto a commercialn-type silicon substrate using pulsed laser deposition (PLD) technique. The structural properties of the PLD-grownp-NiO material were analysed by means of x-ray diffraction and x-ray photoelectron spectroscopy, confirming its crystalline nature and revealing the presence of Ni vacancies, respectively. Hall measurements confirmed thep-type semiconducting nature of the NiO thin film having a carrier concentration of 8.4 × 1016cm-3. The current-voltage (I-V) characteristics of thep-NiO/n-Si heterojunction photodevice were investigated under different wavelengths ranging from UV to NIR. The self-bias properties under different illuminations of light were also explored systematically. Under self-bias condition, the photodiode exhibits excellent responsivities of 12.5 mA W-1, 24.6 mA W-1and 30.8 mA W-1with illumination under 365 nm, 485 nm, and 850 nm light, respectively. In addition, the time dependency of the photoresponse of the fabricated photodevice has also been investigated and discussed thoroughly.

Emotional processing during the therapy for complicated grief.

OBJECTIVE: Prior research, mainly conducted on depression, observed that clients' improved capability to process their emotions predicted better therapeutic outcomes. The current comparative study aimed to investigate whether emotional processing was related to therapeutic change in complicated grief. METHOD: We analyzed two contrasting cases (good or poor outcome) treated with grief constructivist therapy. In both cases we investigated the association of emotional processing (Experiencing Scale) to (1) therapeutic outcome (Inventory of Complicated Grief), and (2) change in the type of grief-related emotions (Emotions Episodes). RESULTS: The session-by-session growth of clients' emotional processing and the change of grief-related emotions were qualitatively explored throughout both cases. Compared with the poor outcome case, the good outcome case achieved more improvement in the ability to process emotions. Such improvement occurred alongside a deeper change in the type of grief-related emotions aroused, from maladaptive to more adaptive responses. CONCLUSION: Our findings suggest that a higher emotional processing capability may be associated with the transformation of grief-related maladaptive emotions and with the improvement of complicated grief condition.

Nanocomposite Polymer Electrolytes of Sodium Alginate and Montmorillonite Clay.

Nanocomposite polymer electrolytes (NPEs) were synthesized using sodium alginate (Alg) and either sodium (SCa-3-Na+)- or lithium (SCa-3-Li+)-modified montmorillonite clays. The samples were characterized by structural, optical, and electrical properties. SCa-3-Na+ and SCa-3-Li+ clays' X-ray structural analyses revealed peaks at 2θ = 7.2° and 6.7° that corresponded to the interlamellar distances of 12.3 and 12.8 Å, respectively. Alg-based NPEs X-ray diffractograms showed exfoliated structures for samples with low clay percentages. The increase of clay content promoted the formation of intercalated structures. Electrochemical Impedance Spectroscopy revealed that Alg-based NPEs with 5 wt% of SCa-3-Na+ clay presented the highest conductivity of 1.96 × 10-2 S/cm2, and Alg with 10 wt% of SCa-3-Li+ showed conductivity of 1.30 × 10-2 S/cm2, both measured at 70 °C. From UV-Vis spectroscopy, it was possible to infer that increasing concentration of clay promoted a decrease of the samples' transmittance and, consequently, an increase of their reflectance.

Non-Newtonian Thermosensitive Nanofluid Based on Carbon Dots Functionalized with Ionic Liquids.

Non-Newtonian nanofluids present outstanding features in terms of energy transfer and conductivity with high application in numerous areas. In this work, non-Newtonian nanofluids based on carbon dots (Cdots) functionalized with ionic liquids (ILs) are developed. The nanofluids are produced using a simple, single-step method where the raw materials for the Cdots synthesis are glucose and waste biomass (chitin from crab shells). The use of ILs as both reaction media and functionalization molecules allows for the development of a new class of nanofluids, where the ILs on the Cdots surface represent the base-fluid. Here, the well-known benign IL 1-butyl-3-methylimidazolium chloride ([Bmim]Cl) and a novel home-made IL (1-tosylate-3-methyl-imidazolium triflate) [Tmi][Trif] are used. The nanofluids obtained from both substrates show, apart from high conductivity and viscosity, light absorption, and good wettability, an appealing thermal sensitivity behavior. This thermal sensitivity is preserved even when applied as thin films on glass slides and can be boosted using the surface plasmon resonance effect. The results reported demonstrate that the new Cdots/IL-based nanofluids constitute a versatile and cost-effective route for achieving high-performance thermosensitive non-Newtonian sustainable nanofluids with tremendous potential for the energy coatings sector and heat transfer film systems.

Chronic hepatitis C treatment in HIV co-infection in Portugal: Results from a cohort OF 2133 patients presented by GEPCOI (Portuguese Coinfection Study Group).

Direct-acting antiviral drugs (DAAs) have recently changed the paradigm of hepatitis C therapy, significantly improving treatment response rates, patient life expectancy and quality of life. In Portugal, sofosbuvir (SOF) and SOF/ledipasvir (SOF/LDV) were fully reimbursed by the National Health System since early 2015 and generalized use of interferon-free DAA based regimens became current practice. During 2016, the remaining DAAs were sequentially added and covered by the same health access policy. The Portuguese Study Group of Hepatitis and HIV Co-infection (GEPCOI) collected data from 15 clinical centres in Portugal, pertaining to the HCV treatment experience with DAA regimens. A cohort of 2133 patients was analysed, representing one of the largest DAA treated HCV/HIV co-infected individuals. The global sustained virologic response (SVR) achieved was 95% in this real-life cohort setting. Linear regression analysis showed significant differences in treatment response rates when using SOF plus ribavirin (RBV) combination in genotype 2 or 3 infected individuals (P < .002) and in those with liver cirrhosis (P < .002). These findings corroborate that early treatment is mandatory in HIV/HCV co-infected patients, as response rates may be negatively influenced by higher fibrosis stages and suboptimal DAA regimens. The current national Portuguese health policy should continue to promote wider treatment access and individualized therapy strategies, aiming at the elimination of HCV infection in this high-risk co-infected population.

Metabolic engineering strategies for butanol production in Escherichia coli.

The global market of butanol is increasing due to its growing applications as solvent, flavoring agent, and chemical precursor of several other compounds. Recently, the superior properties of n-butanol as a biofuel over ethanol have stimulated even more interest. (Bio)butanol is natively produced together with ethanol and acetone by Clostridium species through acetone-butanol-ethanol fermentation, at noncompetitive, low titers compared to petrochemical production. Different butanol production pathways have been expressed in Escherichia coli, a more accessible host compared to Clostridium species, to improve butanol titers and rates. The bioproduction of butanol is here reviewed from a historical and theoretical perspective. All tested rational metabolic engineering strategies in E. coli to increase butanol titers are reviewed: manipulation of central carbon metabolism, elimination of competing pathways, cofactor balancing, development of new pathways, expression of homologous enzymes, consumption of different substrates, and molecular biology strategies. The progress in the field of metabolic modeling and pathway generation algorithms and their potential application to butanol production are also summarized here. The main goals are to gather all the strategies, evaluate the respective progress obtained, identify, and exploit the outstanding challenges.

Complete genomic and transcriptional landscape analysis using third-generation sequencing: a case study of Saccharomyces cerevisiae CEN.PK113-7D.

Completion of eukaryal genomes can be difficult task with the highly repetitive sequences along the chromosomes and short read lengths of second-generation sequencing. Saccharomyces cerevisiae strain CEN.PK113-7D, widely used as a model organism and a cell factory, was selected for this study to demonstrate the superior capability of very long sequence reads for de novo genome assembly. We generated long reads using two common third-generation sequencing technologies (Oxford Nanopore Technology (ONT) and Pacific Biosciences (PacBio)) and used short reads obtained using Illumina sequencing for error correction. Assembly of the reads derived from all three technologies resulted in complete sequences for all 16 yeast chromosomes, as well as the mitochondrial chromosome, in one step. Further, we identified three types of DNA methylation (5mC, 4mC and 6mA). Comparison between the reference strain S288C and strain CEN.PK113-7D identified chromosomal rearrangements against a background of similar gene content between the two strains. We identified full-length transcripts through ONT direct RNA sequencing technology. This allows for the identification of transcriptional landscapes, including untranslated regions (UTRs) (5' UTR and 3' UTR) as well as differential gene expression quantification. About 91% of the predicted transcripts could be consistently detected across biological replicates grown either on glucose or ethanol. Direct RNA sequencing identified many polyadenylated non-coding RNAs, rRNAs, telomere-RNA, long non-coding RNA and antisense RNA. This work demonstrates a strategy to obtain complete genome sequences and transcriptional landscapes that can be applied to other eukaryal organisms.

Domesticated Populations of Codium tomentosum Display Lipid Extracts with Lower Seasonal Shifts than Conspecifics from the Wild-Relevance for Biotechnological Applications of this Green Seaweed.

In the last decades, the use of algae in biotechnology and food industries has experienced an exponential growth. Codium tomentosum is a green macroalgae with high biotechnological potential, due to its rich lipidome, although few studies have addressed it. This study aimed to investigate the seasonal changes in lipid and pigment profiles of C. tomentosum, as well as to screen its antioxidant activity, in order to evaluate its natural plasticity. Samples of C. tomentosum were collected in two different seasons, early-autumn (September/October) and spring (May), in the Portuguese coast (wild samples), and in a land-based integrated multitrophic aquaculture (IMTA) system (IMTA samples). Total lipid extracts were analysed by LC-MS, GC-MS, and HPLC, and antioxidant activity was screened through free radical scavenging potential against DPPH and 2,20-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid (ABTS) radicals. Wild samples showed a high seasonal variability, modifying their lipidome and pigment profiles according to environmental shifts, while IMTA samples showed a relatively stable composition due to early-stage culturing in controlled conditions. The lipids that contributed the most to seasonal discrimination were glycolipids (monogalactosyl diacylglycerol - MGDG and digalactosyl diacylglycerol - DGDG) and the lyso forms of phospholipids and glycolipids. Lipid extracts showed antioxidant activity ranging from 61 ± 2 to 115 ± 35 µmol Trolox g-1 of lipid extract in DPPH assay and from 532 ± 73 to 927 ± 92 µmol Trolox g-1 of lipid extract in ABTS assay, with a more intense antioxidant activity in wild spring samples. This study revealed that wild specimens of C. tomentosum presented a higher plasticity to cope with seasonal environmental changes, adjusting their lipid, pigment, and bioactivity profiles, while IMTA samples, cultured under controlled conditions, displayed more stable lipidome and pigment compositions.

Adaptive laboratory evolution of tolerance to dicarboxylic acids in Saccharomyces cerevisiae.

Improving the growth phenotypes of microbes in high product concentrations is an essential design objective in the development of robust cell factories. However, the limited knowledge regarding tolerance mechanisms makes rational design of such traits complicated. Here, adaptive laboratory evolution was used to explore the tolerance mechanisms that Saccharomyces cerevisiae can evolve in the presence of inhibiting concentrations of three dicarboxylic acids: glutaric acid, adipic acid and pimelic acid. Whole-genome sequencing of tolerant mutants enabled the discovery of the genetic changes behind tolerance and most mutations could be linked to the up-regulation of multidrug resistance transporters. The amplification of QDR3, in particular, was shown to confer tolerance not only to the three dicarboxylic acids investigated, but also towards muconic acid and glutaconic acid. In addition to increased acid tolerance, QDR3 overexpression also improved the production of muconic acid in the context of a strain engineered for producing this compound.

Silk Fibroin Dissolution in Tetrabutylammonium Hydroxide Aqueous Solution.

Bombyx mori L. silk fibroin (SF) is widely used in different areas due to its ability to form durable and resilient materials with notable mechanical properties. However, in some of these applications the dissolution of SF is required, and this is not often straightforward due to its inability to be dissolved in the majority of common solvents. This work reports a novel approach to dissolve SF using 40 wt % aqueous tetrabutylammonium hydroxide, TBAOH(aq), at mild temperature. A thorough rheological study combined with small-angle X-ray scattering is presented to correlate the SF state in solution with changes in the rheological parameters. The scattering data suggest that the SF conformation in TBAOH(aq) is close to a random coil, possibly having some compact domains linked with flexible random chains. The radius of gyration (Rg) and the molecular weight (Mw) were estimated to be ca. 17.5 nm and 450 kDa, respectively, which are in good agreement with previous works. Nevertheless, a lower Mw value was deduced from rheometry (i.e., 321 kDa) demonstrating a low degree of depolymerization during dissolution in comparison to other harsh processes. The transition from a dilute to a semidilute regime coincides with the estimated critical concentration and is marked by the presence of a shear-thinning behavior in the flow curves, violation of the empirical Cox-Merz rule, and an upward increase in the activation energy. This work paves the way toward the development of advanced high-tech SF-based materials.

Why co-catalyst-loaded rutile facilitates photocatalytic hydrogen evolution.

As the conduction band edge of rutile is close to the reduction potential of hydrogen, there is a long-lasting discussion on whether molecular hydrogen can be evolved from this semiconductor. Our study on methanol photoreforming in the ultra-high vacuum reveals that photocatalysts comprising a TiO2(110) single crystal decorated with platinum clusters indeed enable the evolution of H2. This is attributed to a new type of mechanism, in which the co-catalyst acts as a recombination center for hydrogen and not as a reduction site of a photoreaction. This mechanism is an alternative pathway to the commonly used mechanism derived from photoelectrochemistry and must particularly be considered for systems, in which reducible semiconductors enable the surface diffusion of hydrogen species.

A New Look for the Red Macroalga Palmaria palmata: A Seafood with Polar Lipids Rich in EPA and with Antioxidant Properties.

Palmaria palmata is an edible red macroalga widely used for human consumption and valued for its high protein value. Despite its low total lipid content, it is rich in eicosapentaenoic acid (EPA). This seaweed has been scarcely explored with regard to its lipid composition. The polar lipids of seaweeds are nowadays recognized as important phytochemicals contributing to their add value valorization and providing support for claims of potential health benefits. The present study aimed to disclose the polar lipid profile of P. palmata, farmed in an integrated multi-trophic aquaculture (IMTA) through modern lipidomic approaches using high-resolution LC-MS and MS/MS and to screen for the antioxidant properties of this red macroalga. A total of 143 molecular species of lipids were identified, belonging to several classes of polar lipids, such as glycolipids, phospholipids, and betaine lipids. It is noteworthy that the most abundant lipid species in each class were esterified with eicosapentaenoic acid (EPA), accounting for more than 50% of the lipid content. The polar lipid extract rich in EPA showed antioxidant activity with an inhibition concentration (IC) of IC30 = 171 ± 19.8 µg/mL for α,α-diphenyl-ß-picrylhydrazyl radical (DPPH●) and IC50 = 26.2 ± 0.1 µg/mL for 2,20-azino-bis-3-ethylbenzothiazoline-6-sulfonic acid radical cation (ABTS●+). Overall, this study highlights that P. palmata farmed in an IMTA framework can be a sustainable source of beneficial lipids with antioxidant activity. Moreover, this red macroalga can be exploited for future applications as a source of lipids rich in EPA for food and feed, nutraceuticals, and cosmetics.

Lipidomic Signatures Reveal Seasonal Shifts on the Relative Abundance of High-Valued Lipids from the Brown Algae Fucus vesiculosus.

Fucus vesiculosus is an edible brown macroalga, with health benefits associated with its consumption and also a source of bioactive molecules. It is acknowledged that the biochemical composition of macroalgae changes when exposed to different environmental conditions occurring on different habitats, such as the water temperature, and light intensity. In the present study, the polar lipidome of Fucus vesiculosus was characterized for the first time using modern high-resolution HILIC-MS, and MS/MS approaches, to evaluate the phenotypic variability in two seasons of the year, e.g., winter and spring. A total of 187 molecular species were identified over eighteen classes of glycolipids, phospholipids and betaine lipids. Principal component analysis (PCA) multivariate statistical analysis and cluster analysis of polar lipid classes, polar lipid species and total fatty acids (FA) datasets, showed clustering according to the seasonal groups. While the lipid profile of Fucus vesiculosus harvested in the winter and spring yielded the same molecular species, the relative abundance of these species was significantly different. In the winter, changes were mainly due to the increased relative abundance of some molecular species of glycolipids and phospholipids, bearing octadeca(poly)enoic (18:3, 18:4) and eicosa(poly)enoic (20:4, 20:5) FA and betaine lipids species with short saturated FA (14:0) and polyunsaturated FA (PUFA). Importantly, glycolipids with n-3 PUFA and sulfolipids, have been reported to have important biological activities and therapeutic value. Overall, Fucus vesiculosus is a promising source of bioactive compounds that can be used as functional food or ingredients for human nutrition, feed, pharma, and cosmetic formulations. In this study, samples harvested in the winter season maximized yields of these bioactive components, when compared with samples harvested in the spring.

Dietary Supplementation with the Red Seaweed Porphyra umbilicalis Protects against DNA Damage and Pre-Malignant Dysplastic Skin Lesions in HPV-Transgenic Mice.

Some diet profiles are associated with the risk of developing cancer; however, some nutrients show protective effects. Porphyra umbilicalis is widely consumed, having a balanced nutritional profile; however, its potential for cancer chemoprevention still needs comprehensive studies. In this study, we incorporated P. umbilicalis into the diet of mice transgenic for the human papillomavirus type 16 (HPV16), which spontaneously develop pre-malignant and malignant lesions, and determined whether this seaweed was able to block lesion development. Forty-four 20-week-old HPV+/- and HPV-/- mice were fed either a base diet or a diet supplemented with 10% seaweed. At the end of the study, skin samples were examined to classify HPV16-induced lesions. The liver was also screened for potential toxic effects of the seaweed. Blood was used to study toxicological parameters and to perform comet and micronucleus genotoxicity tests. P. umbilicalis significantly reduced the incidence of pre-malignant dysplastic lesions, completely abrogating them in the chest skin. These results suggest that P. umbilicalis dietary supplementation has the potential to block the development of pre-malignant skin lesions and indicate its antigenotoxic activity against HPV-induced DNA damage. Further studies are needed to establish the seaweed as a functional food and clarify the mechanisms whereby this seaweed blocks multistep carcinogenesis induced by HPV.