Genomic exploration of the fermented meat isolate Staphylococcus shinii IMDO-S216 with a focus on competitiveness-enhancing secondary metabolites.

BACKGROUND: Staphylococcus shinii appears as an umbrella species encompassing several strains of Staphylococcus pseudoxylosus and Staphylococcus xylosus. Given its phylogenetic closeness to S. xylosus, S. shinii can be found in similar ecological niches, including the microbiota of fermented meats where the species may contribute to colour and flavour development. In addition to these conventional functionalities, a biopreservation potential based on the production of antagonistic compounds may be available. Such potential, however, remains largely unexplored in contrast to the large body of research that is available on the biopreservative properties of lactic acid bacteria. The present study outlines the exploration of the genetic basis of competitiveness and antimicrobial activity of a fermented meat isolate, S. shinii IMDO-S216. To this end, its genome was sequenced, de novo assembled, and annotated. RESULTS: The genome contained a single circular chromosome and eight plasmid replicons. Focus of the genomic exploration was on secondary metabolite biosynthetic gene clusters coding for ribosomally synthesized and posttranslationally modified peptides. One complete cluster was coding for a bacteriocin, namely lactococcin 972; the genes coding for the pre-bacteriocin, the ATP-binding cassette transporter, and the immunity protein were also identified. Five other complete clusters were identified, possibly functioning as competitiveness factors. These clusters were found to be involved in various responses such as membrane fluidity, iron intake from the medium, a quorum sensing system, and decreased sensitivity to antimicrobial peptides and competing microorganisms. The presence of these clusters was equally studied among a selection of multiple Staphylococcus species to assess their prevalence in closely-related organisms. CONCLUSIONS: Such factors possibly translate in an improved adaptation and competitiveness of S. shinii IMDO-S216 which are, in turn, likely to improve its fitness in a fermented meat matrix.

Decarboxylase activity of the non-starter lactic acid bacterium Loigolactobacillus rennini gives crack defects in Gouda cheese through the production of γ-aminobutyric acid.

Ten Gouda cheese wheels with an age of 31 weeks from six different batch productions were affected by a crack defect and displayed an unpleasant off-flavor. To unravel the causes of these defects, the concentrations of free amino acids, other organic acids, volatile organic compounds, and biogenic amines were quantified in zones around the cracks and in zones without cracks, and compared with those of similar Gouda cheeses without crack defect. The Gouda cheeses with cracks had a significantly different metabolome. The production of the non-proteinogenic amino acid γ-aminobutyric acid (GABA) could be unraveled as the key mechanism leading to crack formation, although the production of the biogenic amines cadaverine and putrescine contributed as well. High-throughput amplicon sequencing of the full-length 16S rRNA gene based on whole-community DNA revealed the presence of Loigolactobacillus rennini and Tetragenococcus halophilus as most abundant non-starter lactic acid bacteria in the zones with cracks. Shotgun metagenomic sequencing allowed to obtain a metagenome-assembled genome of both Loil. rennini and T. halophilus. However, only Loil. rennini contained genes necessary for the production of GABA, cadaverine, and putrescine. Metagenetics further revealed the brine and the rennet used during cheese manufacturing as the most plausible inoculation sources of both Loil. rennini and T. halophilus.IMPORTANCECrack defects in Gouda cheeses are still poorly understood, although they can lead to major economic losses in cheese companies. In this study, the bacterial cause of a crack defect in Gouda cheeses was identified, and the pathways involved in the crack formation were unraveled. Moreover, possible contamination sources were identified. The brine bath might be a major source of bacteria with the potential to deteriorate cheese quality, which suggests that cheese producers should regularly investigate the quality and microbial composition of their brines. This study illustrated how a multiphasic approach can understand and mitigate problems in a cheese company.

An in-depth multiphasic analysis of the chocolate production chain, from bean to bar, demonstrates the superiority of Saccharomyces cerevisiae over Hanseniaspora opuntiae as functional starter culture during cocoa fermentation.

Hanseniaspora opuntiae is a commonly found yeast species in naturally fermenting cocoa pulp-bean mass, which needed in-depth investigation. The present study aimed at examining effects of the cocoa isolate H. opuntiae IMDO 040108 as part of three different starter culture mixtures compared with spontaneous fermentation, regarding microbial community, substrate consumption, and metabolite production dynamics, including volatile organic compound (VOC) and phytochemical compositions, as well as compositions of the cocoa beans after fermentation, cocoa liquors, and chocolates. The inoculated H. opuntiae strain was unable to prevail over background yeasts present in the fermenting cocoa pulp-bean mass. It led to under-fermented cocoa beans after four days of fermentation, which was however reflected in higher levels of polyphenols. Cocoa fermentation processes inoculated with a Saccharomyces cerevisiae strain enhanced flavour production during the fermentation and drying steps, which was reflected in richer and more reproducible aroma profiles of the cocoa liquors and chocolates. Sensory analysis of the cocoa liquors and chocolates further demonstrated that S. cerevisiae led to more acidic notes compared to spontaneous fermentation, as a result of an advanced fermentation degree. Finally, different VOC profiles were found in the cocoa beans throughout the whole chocolate production chain, depending on the fermentation process.

Functional yeast starter cultures for cocoa fermentation.

The quest to develop a performant starter culture mixture to be applied in cocoa fermentation processes started in the 20th century, aiming at achieving high-quality, reproducible chocolates with improved organoleptic properties. Since then, different yeasts have been proposed as candidate starter cultures, as this microbial group plays a key role during fermentation of the cocoa pulp-bean mass. Yeast starter culture-initiated fermentation trials have been performed worldwide through the equatorial zone and the effects of yeast inoculation have been analysed as a function of the cocoa variety (Forastero, Trinitario and hybrids) and fermentation method (farm-, small- and micro-scale) through the application of physicochemical, microbiological and chemical techniques. A thorough screening of candidate yeast starter culture strains is sometimes done to obtain the best performing strains to steer the cocoa fermentation process and/or to enhance specific features, such as pectinolysis, ethanol production, citrate assimilation and flavour production. Besides their effects during cocoa fermentation, a significant influence of the starter culture mixture applied is often found on the cocoa liquors and/or chocolates produced thereof. Thus, starter culture-initiated cocoa fermentation processes constitute a suitable strategy to elaborate improved flavourful chocolate products.

"Therapeutic uses of natural astaxanthin: An evidence-based review focused on human clinical trials".

Astaxanthin is a natural C40 carotenoid with numerous reported biological functions, most of them associated with its antioxidant and anti-inflammatory activity, standing out from other antioxidants as it has shown the highest oxygen radical absorbance capacity (ORAC), 100-500 times higher than ⍺-tocopherol and a 10 times higher free radical inhibitory activity than related antioxidants (α-tocopherol, α-carotene, ß -carotene, lutein and lycopene). In vitro and in vivo studies have associated astaxanthin's unique molecular features with several health benefits, including neuroprotective, cardioprotective and antitumoral properties, suggesting its therapeutic potential for the prevention or co-treatment of dementia, Alzheimer, Parkinson, cardiovascular diseases and cancer. Benefits on skin and eye health promotion have also been reported, highlighting its potential for the prevention of skin photo-aging and the treatment of eye diseases like glaucoma, cataracts and uveitis. In this review, we summarize and discuss the currently available evidence on astaxanthin benefits, with a particular focus on human clinical trials, including a brief description of the potential mechanisms of action responsible for its biological activities.

Impact of Visual Biofeedback of Trunk Sway Smoothness on Motor Learning during Unipedal Stance.

The assessment of trunk sway smoothness using an accelerometer sensor embedded in a smartphone could be a biomarker for tracking motor learning. This study aimed to determine the reliability of trunk sway smoothness and the effect of visual biofeedback of sway smoothness on motor learning in healthy people during unipedal stance training using an iPhone 5 measurement system. In the first experiment, trunk sway smoothness in the reliability group (n = 11) was assessed on two days, separated by one week. In the second, the biofeedback group (n = 12) and no-biofeedback group (n = 12) were compared during 7 days of unipedal stance test training and one more day of retention (without biofeedback). The intraclass correlation coefficient score 0.98 (0.93-0.99) showed that this method has excellent test-retest reliability. Based on the power law of practice, the biofeedback group showed greater improvement during training days (p = 0.003). Two-way mixed analysis of variance indicates a significant difference between groups (p < 0.001) and between days (p < 0.001), as well as significant interaction (p < 0.001). Post hoc analysis shows better performance in the biofeedback group from training days 2 and 7, as well as on the retention day (p < 0.001). Motor learning objectification through visual biofeedback of trunk sway smoothness enhances postural control learning and is useful and reliable for assessing motor learning.

Bona fide evidence for natural vertical transmission of infectious salmon anemia virus in freshwater brood stocks of farmed Atlantic salmon (Salmo salar) in Southern Chile.

UNLABELLED: Infectious salmon anemia (ISA) is a severe disease that affects farmed Atlantic salmon (Salmo salar), causing outbreaks in seawater in most salmon-producing countries worldwide, with particular aggressiveness in southern Chile. The etiological agent of this disease is a virus belonging to the Orthomyxoviridae family, named infectious salmon anemia virus (ISAV). Although it has been suggested that this virus can be vertically transmitted, even in freshwater, there is a lack of compelling experimental evidence to confirm this. Here we demonstrate significant putative viral loads in the ovarian fluid as well as in the eggs of two brood stock female adult specimens that harbored the virus systemically but without clinical signs. The target virus corresponded to a highly polymorphic region 3 (HPR-3) variant, which is known to be virulent in seawater and responsible for recent and past outbreaks of this disease in Chile. Additionally, the virus recovered from the fluid as well as from the interior of the eggs was fully infective to a susceptible fish cell line. To our knowledge, this is the first robust evidence demonstrating mother-to-offspring vertical transmission of the infective virus on the one hand and the asymptomatic transmission of a virulent form of the virus in freshwater fish on the other hand. IMPORTANCE: The robustness of the data presented here will contribute to a better understanding of the biology of the virus but most importantly will constitute a key management tool in the control of an aggressive agent constantly threatening the sustainability of the global salmon industry.

Clinical and molecular characterization of a patient with 15q21.2q22.2 deletion syndrome.

We report on a 16-year-old girl with a complex phenotype, including intellectual disability, facial dysmorphisms, and obesity. During her infancy, she presented with weak sucking, global developmental delay, and later with excessive eating with central obesity. The girl was clinically diagnosed with probable Prader-Willi syndrome. Chromosomal analysis showed a de novo deletion 46,XX,del(15)(q21q22). However, the use of the Affymetrix CytoScan HD Array defined the exact breakpoints of the deleted 15q21q22 region. The imbalance, about 10.5 Mb in size, is to date the second largest deletion ever described in this chromosomal region. In addition, our patient carries a microdeletion in the 1q44 region and a gain in 9p24. The array result was arr[hg19] 9p24.1(6,619,823-6,749,335)×3, 1q44(248,688,586-248,795,277)×1, 15q21.2 q22.2(50,848,301-61,298,006)×1. Although our patient presents additional chromosomal alterations, we provide a correlation between the clinical findings and the phenotype of the 15q21 deletion syndrome.

Monitoring SpO2: The Basics of Retinopathy of Prematurity (Back to Basics) and Targeting Oxygen Saturation.

Oxygen (O2) is a drug frequently used in newborn care. Adverse effects of hypoxia are well known but the damaging effects of excess oxygen administration and oxidative stress have only been studied in the last 2 decades. Many negative effects have been described, including retinopathy of prematurity . Noninvasive pulse oximetry (SpO2) is useful to detect hypoxemia but requires careful evaluation and understanding of the frequently changing relationship between O2 and hemoglobin to prevent hyperoxemia. Intention to treat SpO2 ranges should be individualized for every newborn receiving supplemental O2, according to gestational age, post-natal age, and clinical condition.

End-of-life care in neonatal intensive care units in Iberoamerica: A look from the nursing perspective.

INTRODUCTION: End-of-life care (ELC) represents a quality milestone in neonatal intensive care units (NICU). The objective of this study was to explore how ELC are carried out in NICUs in Iberoamerica. METHODS: Cross-sectional study, through the administration of an anonymous survey sent to neonatal nursing professionals. The survey included general data and work activity data; existence and contents of ELC protocols in the NICU and training received. The survey was distributed by email and published on official SIBEN social networks. REDCap and STATA 14.0 software were used for data collection and analysis. RESULTS: We obtained 400 responses from nurses from 11 countries in the Ibero-American region. 86% of the respondents are directly responsible for providing ELC, although 48% of them said they had not received training on this subject. Only 67 (17%) state that the NICU in which they work has a protocol that establishes a strategy for performing the ELC. Finally, the actions that are implemented during the ELC are globally infrequent (≤50%) in all the items explored and very infrequent (<20%) in relation to allowing free access to family members, having privacy, providing psychological assistance, register the process in the medical record, assist with bureaucratic processes or grant a follow-up plan for grief. CONCLUSION: Most of the nursing professionals surveyed are directly responsible for this care, do not have protocols, have not received training, and consider that the ELC could be significantly improved. Strategies for ELCs in the Ibero-American region need to be optimized.

Exposure to fine particulate matter 2.5 from wood combustion smoke causes vascular changes in placenta and reduce fetal size.

During gestation, maternal blood flow to the umbilical cord and placenta increases, facilitating efficient nutrient absorption, waste elimination, and effective gas exchange for the developing fetus. However, the effects of exposure to wood smoke during this period on these processes are unknown. We hypothesize that exposure to PM2.5, primarily sourced from wood combustion for home heating, affects placental vascular morphophysiology and fetal size. We used exposure chambers that received either filtered or unfiltered air. Female rats were exposed to PM2.5 during pre-gestational and/or gestational stages. Twenty-one days post-fertilization, placentas were collected via cesarean section. In these placentas, oxygen diffusion capacity was measured, and the expression of angiogenic factors was analyzed using qPCR and immunohistochemistry. In groups exposed to PM2.5 during pre-gestational and/or gestational stages, a decrease in fetal weight, crown-rump length, theoretical and specific diffusion capacity, and an increase in HIF-1α expression were observed. In groups exposed exclusively to PM2.5 during the pre-gestational stage, there was an increase in the expression of placental genes Flt-1, Kdr, and PIGF. Additionally, in the placental labyrinth region, the expression of angiogenic factors was elevated. Changes in angiogenesis and angiogenic factors reflect adaptations to hypoxia, impacting fetal growth and oxygen supply. In conclusion, this study demonstrates that exposure to PM2.5, emitted from wood smoke, in both pre-gestational and gestational stages, affects fetal development and placental health. This underscores the importance of addressing air pollution in areas with high levels of wood smoke, which poses a significant health risk to pregnant women and their fetuses.

Portal Vein Thrombosis in Liver Transplantation: A Retrospective Cohort Study.

Portal vein thrombosis was considered a contraindication for liver transplantation. This study analyzes the perioperative complications and survival of liver transplant patients with portal vein thrombosis (PVT). A retrospective observational cohort study of liver transplant patients was conducted. The outcomes were early mortality (30 days) and patient survival. A total of 201 liver transplant patients were identified and 34 (17%) patients with PVT were found. The most frequent extension of thrombosis was Yerdel 1 (58.8%), and a portosystemic shunt was identified in 23 (68%) patients. Eleven patients (33%) presented any early vascular complication, PVT being the most frequent (12%). The multivariate regression analysis showed a statistically significant association between PVT and early complications (OR = 3.3, 95% confidence interval 1.4-7.7; p = 0.006). Moreover, early mortality was observed in eight patients (24%), of which two (5.9%) presented Yerdel 2. For Yerdel 1, patient survival according to the extent of thrombosis was 75% at 1 year and 3 years, while for Yerdel 2, it was 65% at 1 year, and 50% at 3 years (p = 0.04). Portal vein thrombosis significantly influenced early vascular complications. Furthermore, portal vein thrombosis Yerdel 2 or higher impacts the survival of liver grafts in the short and long term.

Wernicke's Encephalopathy in a Patient With Type III Intestinal Failure: A Case Report.

This case is about a 38-year-old male patient with a history of type III intestinal failure due to chronic intestinal pseudo-obstruction caused by gastrointestinal dysmotility, cardiac and intestinal arrhythmia syndrome, dependence on parenteral nutrition, sinus dysfunction, and carrying a pacemaker. The patient presented with symptoms suggestive of a new episode of intestinal obstruction. A contrast-enhanced abdominal computed tomography scan was performed, revealing intestinal obstruction with a transition zone in the jejunum. Non-operative medical management of the obstructive condition was initiated. However, after 10 days of medical management, the patient began experiencing nausea and dizziness. Initially, symptomatic management was provided, but the patient reported persistent vertigo-like sensations. Following evaluation by multiple specialties, magnetic resonance imaging (MRI) was requested, which showed bilateral and symmetrical hyperintensity on T2-weighted images of the dorsomedial aspect of the thalami around the third ventricle, in the periaqueductal gray matter, the mesencephalic tectum, and, to a lesser extent, the bulbar tectum, findings suggestive of Wernicke's encephalopathy. Urgent intravenous thiamine replacement was initiated. After 10 days of effective treatment, the patient exhibited a nearly complete improvement in symptoms. A follow-up MRI was ordered, indicating considerable improvement when compared to the previous study.

Photoautotrophic removal of hydrogen sulfide from biogas using purple and green sulfur bacteria.

Biogas desulfurization based on anoxygenic photosynthetic processes represents an alternative to physicochemical technologies, decreasing the risk of O2 and N2 contamination. This work aimed at assessing the potential of Allochromatium vinosum and Chlorobium limicola for biogas desulfurization under different light intensities (10 and 25 klx) and H2S concentrations (1 %, 1.5 % and 2 %) in batch photobioreactors. In addition, the influence of rising biogas flow rates (2.9, 5.8 and 11.5 L d-1 in stage I, II and III, respectively) on the desulfurization performance in a 2.3 L photobioreactor utilizing C. limicola under continuous mode was assessed. The light intensity of 25 klx negatively influenced the growth of A. vinosum and C. limicola, resulting in decreased H2S removal capacity. An increase in H2S concentrations resulted in higher volumetric H2S removal rates in C. limicola (2.9-5.3 mg L-1 d-1) tests compared to A. vinosum (2.4-4.6 mg L-1 d-1) tests. The continuous photobioreactor completely removed H2S from biogas in stage I and II. The highest flow rate in stage III induced a deterioration in the desulfurization activity of C. limicola. Overall, the high H2S tolerance of A. vinosum and C. limicola supports their use in H2S desulfurization from biogas.

Seaweeds in Food: Current Trends.

Edible seaweeds are an excellent source of macronutrients, micronutrients, and bioactive compounds, and they can be consumed raw or used as ingredients in food products. However, seaweeds may also bioaccumulate potentially hazardous compounds for human health and animals, namely, heavy metals. Hence, the purpose of this review is to analyze the recent trends of edible seaweeds research: (i) nutritional composition and bioactive compounds, (ii) the use and acceptability of seaweeds in foodstuffs, (iii) the bioaccumulation of heavy metals and microbial pathogens, and (iv) current trends in Chile for using seaweeds in food. In summary, while it is evident that seaweeds are consumed widely worldwide, more research is needed to characterize new types of edible seaweeds as well as their use as ingredients in the development of new food products. Additionally, more research is needed to maintain control of the presence of heavy metals to assure a safe product for consumers. Finally, the need to keep promoting the benefits of seaweed consumption is emphasized, adding value in the algae-based production chain, and promoting a social algal culture.

Yeast strains do have an impact on the production of cured cocoa beans, as assessed with Costa Rican Trinitario cocoa fermentation processes and chocolates thereof.

The microbiological and metabolic outcomes of good cocoa fermentation practices can be standardized and influenced through the addition of starter culture mixtures composed of yeast and bacterial strains. The present study performed two spontaneous and 10 starter culture-initiated (SCI) cocoa fermentation processes (CFPs) in Costa Rica with local Trinitario cocoa. The yeast strains Saccharomyces cerevisiae IMDO 050523, Hanseniaspora opuntiae IMDO 020003, and Pichia kudriavzevii IMDO 060005 were used to compose starter culture mixtures in combination with the lactic acid bacterium strain Limosilactobacillus fermentum IMDO 0611222 and the acetic acid bacterium strain Acetobacter pasteurianus IMDO 0506386. The microbial community and metabolite dynamics of the cocoa pulp-bean mass fermentation, the metabolite dynamics of the drying cocoa beans, and the volatile organic compound (VOC) profiles of the chocolate production were assessed. An amplicon sequence variant approach based on full-length 16S rRNA gene sequencing instead of targeting the V4 region led to a highly accurate monitoring of the starter culture strains added, in particular the Liml. fermentum IMDO 0611222 strain. The latter strain always prevailed over the background lactic acid bacteria. A similar approach, based on the internal transcribed spacer (ITS1) region of the fungal rRNA transcribed unit, was used for yeast strain monitoring. The SCI CFPs evolved faster when compared to the spontaneous ones. Moreover, the yeast strains applied did have an impact. The presence of S. cerevisiae IMDO 050523 was necessary for successful fermentation of the cocoa pulp-bean mass, which was characterized by the production of higher alcohols and esters. In contrast, the inoculation of H. opuntiae IMDO 020003 as the sole yeast strain led to underfermentation and a poor VOC profile, mainly due to its low competitiveness. The P. kudriavzevii IMDO 060005 strain tested in the present study did not contribute to a richer VOC profile. Although differences in VOCs could be revealed in the cocoa liquors, no significant effect on the final chocolates could be obtained, mainly due to a great impact of cocoa liquor processing during chocolate-making. Hence, optimization of the starter culture mixture and cocoa liquor processing seem to be of pivotal importance.

Comparison of Outcomes and Survival of Two Cohorts of Patients with Simultaneous Pancreas-Kidney Transplantation: A Retrospective Cohort Study in a Latin American Hospital.

Background: Simultaneous pancreas-kidney transplantation (SPKT) is a complex and demanding procedure with a considerable risk of morbidity and mortality. Advances in surgical techniques and organ preservation have introduced changes in care protocols. Two cohorts of patients receiving SPKT with two different protocols were compared to determine overall survival and pancreatic and renal graft failure-free survival. Methods: This retrospective observational study was conducted in two cohorts of SPKT recipient patients that underwent surgery between 2001 and 2021. Outcomes were compared in transplant patients between 2001 and 2011 (cohort 1; initial protocol) and 2012-2021 (cohort 2; improved protocol). In addition to the temporality, the cohorts were defined by a protocolization of technical aspects and medical management in cohort 2 (improved protocol), compared to a wide variability in the procedures carried out in cohort 1 (initial protocol). Overall survival and pancreatic and renal graft failure-free survival were the primary outcomes. These outcomes were determined using Kaplan-Meier survival analysis and the log-rank test. Results: Fifty-five SPKT were performed during the study period: 32 in cohort 1 and 23 in cohort 2. In the survival analysis, an average of 2546 days (95% CI: 1902-3190) was found in cohort 1, while in cohort 2, it was 2540 days (95% CI: 2100-3204) (p > 0.05). Pancreatic graft failure-free survival had an average of 1705 days (95% CI: 1037-2373) in cohort 1, lower than the average in cohort 2 (2337 days; 95% CI: 1887-2788) (p = 0.016). Similarly, renal graft failure-free survival had an average of 2167 days (95% CI: 1485-2849) in cohort 1, lower than the average in cohort 2 (2583 days; 95% CI: 2159-3006) (p = 0.017). Conclusions: This analysis indicates that pancreatic and renal graft failure-free survival associated with SPKT decreased significantly in cohort 2, with results related to improvements in the treatment protocol implemented in that cohort.

Antiviral activity of red algae phycocolloids against herpes simplex virus type 2 in vitro.

Herpes simplex virus type 2 (HSV-2) is a human infectious agent with significant impact on public health due to its high prevalence in the population and its ability to elicit a wide range of diseases, from mild to severe. Although several antiviral drugs, such as acyclovir, are currently available to treat HSV-2-related clinical manifestations, their effectiveness is poor. Therefore, the identification and development of new antiviral drugs against HSV-2 is necessary. Seaweeds are attractive candidates for such purposes because they are a vast source of natural products due to their highly diverse compounds, many with demonstrated biological activity. In this study, we evaluated the in vitro antiviral potential of red algae extracts obtained from Agarophyton chilense, Mazzaella laminarioides, Porphyridium cruentum, and Porphyridium purpureum against HSV-2. The phycocolloids agar and carrageenan obtained from the macroalgae dry biomass of A. chilense and M. laminarioides and the exopolysaccharides from P. cruentum and P. purpureum were evaluated. The cytotoxicity of these extracts and the surpluses obtained in the extraction process of the agar and carrageenans were evaluated in human epithelial cells (HeLa cells) in addition to their antiviral activity against HSV-2, which were used to calculate selectivity indexes (SIs). Several compounds displayed antiviral activity against HSV-2, but carrageenans were not considered as a potential antiviral therapeutic agent when compared to the other algae extracts with a SI of 23.3. Future assays in vivo models for HSV-2 infection should reveal the therapeutic potential of these algae compounds as new antivirals against this virus.

CRISPR-Cas9-mediated somatic correction of a one-base deletion in the Ugt1a gene ameliorates hyperbilirubinemia in Crigler-Najjar syndrome mice.

(AAV)-mediated episomal gene replacement therapy for monogenic liver disorders is currently limited in pediatric settings due to the loss of vector DNA, associated with hepatocyte duplication during liver growth. Genome editing is a promising strategy leading to a permanent and specific genome modification that is transmitted to daughter cells upon proliferation. Using genome targeting, we previously rescued neonatal lethality in mice with Crigler-Najjar syndrome. This rare monogenic disease is characterized by severe neonatal unconjugated hyperbilirubinemia, neurological damage, and death. Here, using the CRISPR-Staphylococcus aureus Cas9 (SaCas9) platform, we edited the disease-causing mutation present in the Ugt1a locus of these mice. Newborn mice were treated with two AAV8 vectors: one expressing the SaCas9 and single guide RNA, and the other carrying the Ugt1a homology regions with the corrected sequence, while maintained in a temporary phototherapy setting rescuing mortality. We observed a 50% plasma bilirubin reduction that remained stable for up to 6 months. We then tested different Cas9:donor vector ratios, with a 1:5 ratio showing the greatest efficacy in lowering plasma bilirubin, with partial lethality rescue when more severe, lethal conditions were applied. In conclusion, we reduced plasma bilirubin to safe levels and partially rescued neonatal lethality by correcting the mutant Ugt1a1 gene of a Crigler-Najjar mouse model.

Phylogenomics of a Saccharomyces cerevisiae cocoa strain reveals adaptation to a West African fermented food population.

Various yeast strains have been proposed as candidate starter cultures for cocoa fermentation, especially strains of Saccharomyces cerevisiae. In the current study, the genome of the cocoa strain S. cerevisiae IMDO 050523 was unraveled based on a combination of long- and short-read sequencing. It consisted of 16 nuclear chromosomes and a mitochondrial chromosome, which were organized in 20 contigs, with only two small gaps. A phylogenomic analysis of this genome together with another 105 S cerevisiae genomes, among which 20 from cocoa strains showed a geographical distribution of the latter, including S. cerevisiae IMDO 050523. Its genome clustered together with that of a West African fermented food population, indicating a wider adaptation to West African food niches than cocoa. Furthermore, S. cerevisiae IMDO 050523 contained genetic signatures involved in sucrose hydrolysis, pectin degradation, osmotolerance, and conserved amino acid changes in key ester-producing enzymes that could point toward specific niche adaptations.