Detection of plastic, cellulosic micro-fragments and microfibers in Laternula elliptica from King George Island (Maritime Antarctica).

It is generally acknowledged that microplastic pollutants are prevalent in ocean waters and sediments across a range of tropical, temperate, subpolar, and polar regions. The waters surrounding King George Island are significantly impacted by human activities, particularly those related to scientific stations, fishing, and tourism. Organisms, such as Laternula elliptica, can be used as environmental monitors due to the likelihood that they will bioaccumulate pollutants. The goal of this study was to quantify and identify plastic and cellulosic micro-fragments and microfibers present in the soft body of clams (n = 21), collected from Fildes Bay near sewage and wastewater discharges. Plastic and cellulose microfragments and microfibers were counted, and their compositions were determined using FT-IR. All 21 individuals sampled contained fragments and fibers, with a total of 900 items detected (42.86 ± 25.36 mean ± SD items per individual), or 1.82 items g.wet mass-1. 58 % of items were cellulose and 22 % plastic. Considering the plastic polymer compositions, 28.57 % were polyethylene terephthalate (PET), 21.43 % acrylic, 14.29 % high-density polyethylene (HDPE), 14.29 % Polypropylene (PP), 7.14 % ultra-high drawn polyethylene filament (UHMWPE), 7.14 % polyester and 7.14 % Polyethylene. The quantities and prevalence of MP in L. elliptica were higher than those found in other Antarctic marine species, and even in bivalves from populated regions of the world. Our work assessed the pollution status of L. elliptica near an effluent of wastewater plants and found that 95 % of individuals displayed MP and 100 % microfibers that could impact their population.

Microbiome profile of the Antarctic clam Laternula elliptica.

The filter feeder clam Laternula elliptica is a key species in the Antarctic ecosystem. As a stenothermal benthic species, it has a poor capacity for adaptation to small temperature variations. Despite their ecological importance and sensitivity to climate change, studies on their microbiomes are lacking. The goal of this study was to characterize the bacterial communities of L. elliptica and the tissues variability of this microbiome to provide an initial insight of host-microbiota interactions. We investigated the diversity and taxonomic composition of bacterial communities of L. elliptica from five regions of the body using high-throughput 16S rRNA gene sequencing. The results showed that the microbiome of L. elliptica tended to differ from that of the surrounding seawater samples. However, there were no significant differences in the microbial composition between the body sites, and only two OTUs were present in all samples, being considered core microbiome (genus Moritella and Polaribacter). No significant differences were detected in diversity indexes among tissues (mean 626.85 for observed OTUs, 628.89 Chao1, 5.42 Shannon, and 0.87 Simpson). Rarefaction analysis revealed that most tissues reached a plateau of OTU number according to sample increase, with the exception of Siphon samples. Psychromonas and Psychrilyobacter were particularly abundant in L. elliptica whereas Fluviicola dominated seawater and siphons. Typical polar bacteria were Polaribacter, Shewanella, Colwellia, and Moritella. We detected the prevalence of pathogenic bacterial sequences, particularly in the family Arcobacteraceae, Pseudomonadaceae, and Mycoplasmataceae. The prokaryotic diversity was similar among tissues, as well as their taxonomic composition, suggesting a homogeneity of the microbiome along L. elliptica body. The Antarctic clam population can be used to monitor the impact of human activity in areas near Antarctic stations that discharge wastewater.

Outcomes of isolated patellofemoral arthroplasty.

Osteoarthritis of the patellofemoral compartment can cause significant functional impairment. Isolated patellofemoral osteoarthritis affects greater than 10% of males and females over the age of 60. Patellofemoral arthroplasty (PFA) was developed as a joint-preserving procedure that maintains natural knee kinematics in those with isolated patellofemoral disease. First-generation implants were fraught with complications, a high rate of revision, and early conversion to total knee arthroplasty (TKA). Second-generation implants have demonstrated significant improvements in patient-reported outcome measures, complication rates and implant survivorship. Factors that can affect outcomes include surgical indications, patient selection, and PFA prosthesis design. Modern PFA for isolated patellofemoral osteoarthritis has comparable outcomes to TKA for isolated patellofemoral osteoarthritis. In this article, we discuss the use of PFA, implant design, the indications and factors affecting outcomes, and comparison to TKA.

Trophodynamics of the Antarctic toothfish (Dissostichus mawsoni) in the Antarctic Peninsula: Ontogenetic changes in diet composition and prey fatty acid profiles.

The Antarctic toothfish (Dissostichus mawsoni) is the largest notothenioid species in the Southern Ocean, playing a keystone role in the trophic web as a food source for marine mammals and a top predator in deep-sea ecosystems. Most ecological knowledge on this species relies on samples from areas where direct fishing is allowed, whereas in areas closed to fishing, such as the Antarctic Peninsula (AP), there are still key ecological gaps to ensure effective conservation, especially regarding our understanding of its trophic relationships within the ecosystem. Here, we present the first comprehensive study of the feeding behavior of Antarctic toothfish caught in the northern tip of the AP, during two consecutive fishing seasons (2019/20 and 2020/21). Stomach content was analyzed according to size-classes, sex and season. Macroscopic morphological analysis was used to identify prey, whereas DNA analysis was used in highly digested prey items. Fatty acid analysis was conducted to determine the prey's nutritional composition. The diet mainly consisted of Macrouridae, Cephalopoda, Anotopteridae, and Channichthyidae. Other prey items found were crustaceans and penguin remains; however, these were rare in terms of their presence in stomach samples. Sex had no effect on diet, whereas size-class and fishing season influenced prey composition. From 27 fatty acid profiles identified, we observed two different prey groups of fishes (integrated by families Anotopteridae, Macrouridae and Channichthyidae) and cephalopods. Our results revealed a narrow range of prey items typical of a generalist predator, which probably consumes the most abundant prey. Understanding the diet and trophic relationships of Antarctic toothfish is critical for a better comprehension of its role in the benthic-demersal ecosystem of the AP, key for ecosystemic fisheries management, and relevant for understanding and predicting the effect of climate change on this species.

Prevalence of Parent-Reported Food Allergy in a Mexican Pre-School Population.

The magnitude and relevance of food allergies in the preschool population remain unknown in most regions of Mexico and Latin America. Thus, our aim was to estimate the parent-reported prevalence of food allergies in a Mexican preschool population and to characterize their clinical diagnosis and presentation. A cross-sectional survey was conducted in Culiacán City. A validated questionnaire was utilized. A total of 810 parents responded to the questionnaire (valid response rate, 40.7%). The estimated prevalence rates (95% CI) were: "physician-diagnosed Food Allergy (FA), ever" 5.30% (3.86-7.08); "immediate-type FA, ever" 2.96% (1.91-4.38); "immediate-type FA, current" 1.60% (0.86-2.73); and food-dependent anaphylaxis 1.11% (0.51-2.01). The main food allergens were milk (0.49%), strawberries (0.37%), egg, and soy (0.25% each). Atopic diseases and a family history of allergies were significantly associated with immediate-type FA. Among "immediate-type FA, current" cases, 76.9% required emergency room visits, but the prescription of epinephrine autoinjectors was reported in one case only. The food reactions occurred at home (92.35%), in a relative's house (38.5), and at restaurants (23%). Immediate-type FA reactions requiring emergency room visits are not uncommon among the studied population. Actions like proper anaphylaxis management and the prevention of cross-contamination of foods should be encouraged.

Impact of a Nurse-Led Multidisciplinary Heart Failure Clinic in a Low-Resource Setting: Experience in a Latin American Public Healthcare System.

Background: Nurse-led multidisciplinary heart failure clinics (MDHFCs) play an important role in patient care in developed countries, due to their proven benefits relating to mortality, hospitalization, and quality of life. However, evidence is limited regarding the role of MDHFCs in a limited-resource setting. Methods: Patients with heart failure (HF) with reduced ejection fraction (n = 89) were enrolled in a prospective, longitudinal cohort, from January 2018 to January 2019. The following endpoints were collected at baseline and after 6 months of follow-up: (i) quality of life, measured using the Minnesota Living with Heart Failure Questionnaire; (ii) medication adherence using the Morisky Medication Adherence Scale, 8-item; (iii) titration of HF medications; (iv) self-care behavior using the European Heart Failure Self-care Behavior Scale; and (v) mortality and hospitalizations up to 12 months after. Results: The questionnaire score was reduced from 66.5 (interquartile range [IQR], 46-86) at baseline to 26 (IQR, 13-45) at 6 months (P < 0.001). New York Heart Association (NYHA) functional class improved at 6 months (NYHA I: 41.9%; NYHA II: 39.5%; NYHA III: 17.2%), compared to baseline (NYHA I: 20%; NYHA II: 49%; NYHA III: 31%; P < 0.001). Medication adherence using the 8-item Morisky Medication Adherence Scale improved the score from 6 (IQR, 4-7) at baseline to 7 (IQR, 6.25-8; P = 0.001) at 6 months. Uptitration of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (25% vs 18% at target dose) and beta-blockers (25% vs 11% at target dose) was documented. After 6 months of follow-up, the European Heart Failure Self-care Behavior Scale was applied, showing a score of 18.5 (IQR, 15-22). The mortality reported at 12 months of follow-up was 9.7%, and the incidence of hospitalization was 44%. Conclusion: An MDHFC is a feasible strategy to manage an HF clinic in a low-resource setting.

Contexte: Les cliniques multidisciplinaires d'insuffisance cardiaque dirigées par du personnel infirmier jouent un rôle important dans les soins aux patients dans les pays développés en raison de leurs bienfaits démontrés en matière de mortalité, d'hospitalisation, et de qualité de vie. Les preuves quant au rôle de ce type de cliniques dans un contexte de pénurie de ressources sont toutefois limitées. Méthodologie: Des patients atteints d'insuffisance cardiaque (IC) présentant une fraction d'éjection réduite (n = 89) ont été inscrits à une étude de cohortes prospective et longitudinale allant de janvier 2018 à janvier 2019. Les critères d'évaluation suivants ont été mesurés à l'inscription et après six mois de suivi : i) qualité de vie, mesurée par le questionnaire Minnesota Living with Heart Failure Questionnaire; ii) adhésion au traitement médicamenteux, mesuré selon l'échelle en huit points Morisky Medication Adherence Scale; iii) modification de la dose de médicaments contre l'IC; iv) comportements d'autosoins, mesurés selon l'échelle European Heart Failure Self-care Behavior Scale; et v) taux de mortalité et d'hospitalisation jusqu'à 12 mois. Résultats: Le score au questionnaire a diminué pour passer de 66,5 (écart interquartile [EI] : 46 à 86) au départ à 26 (EI : 13 à 45) à six mois (p < 0,001). La catégorie fonctionnelle de la New York Heart Association (NYHA) s'est améliorée à six mois (NYHA I : 41,9 %; NYHA II : 39,5 %; NYHA III : 17,2 %), comparativement au départ (NYHA I : 20 %; NYHA II : 49 %; NYHA III : 31 %; p < 0,001). Le score de l'adhésion au traitement médicamenteux mesuré par l'échelle en huit points Morisky Medication Adherence Scale s'est amélioré, passant de 6 (EI : 4 à 7) au départ à 7 (EI : 6,25 à 8; p = 0,001) à six mois. On a noté une augmentation de la dose d'inhibiteurs de l'enzyme de conversion de l'angiotensine ou de bloqueurs des récepteurs de l'angiotensine (25 % vs 18 % à la dose cible) et de bêtabloquants (25 % vs 11 % à la dose cible). Après six mois de suivi, l'échelle European Heart Failure Self-care Behavior Scale a été appliquée, ce qui a donné un score de 18,5 (EI : 15 à 22). Le taux de mortalité rapporté à 12 mois de suivi était de 9,7 %, et le taux d'hospitalisation était de 44 %. Conclusion: Une clinique multidisciplinaire d'insuffisance cardiaque dirigée par du personnel infirmier est une stratégie réaliste pour gérer une clinique d'IC dans un contexte de pénurie de ressources.

Contrasting environmental conditions precluded lower availability of Antarctic krill affecting breeding chinstrap penguins in the Antarctic Peninsula.

Dramatic decreases of chinstrap penguin populations across the Antarctic Peninsula (AP) are thought to be influenced by climate-driven changes affecting its main prey, the Antarctic krill, however, empirical evidence supporting such hypotheses are scarce. By coupling data on breeding chinstrap penguins, environmental remote sensing and estimates of krill acoustic density, we were able to demonstrate that penguins substantially increased their foraging effort in a year of low krill availability, with consequent reduction in breeding success. A winter of low sea ice cover followed by a summer/spring with stronger wind and lower marine productivity explained the lower and deeper krill availability. Our results highlight the importance of environmental variability on penguin populations, as variability is expected to increase under climate change, affecting foraging behaviour responses.

Sustained IP3-linked Ca2+ signaling promotes progression of triple negative breast cancer cells by regulating fatty acid metabolism.

Rewiring of mitochondrial metabolism has been described in different cancers as a key step for their progression. Calcium (Ca2+) signaling regulates mitochondrial function and is known to be altered in several malignancies, including triple negative breast cancer (TNBC). However, whether and how the alterations in Ca2+ signaling contribute to metabolic changes in TNBC has not been elucidated. Here, we found that TNBC cells display frequent, spontaneous inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ oscillations, which are sensed by mitochondria. By combining genetic, pharmacologic and metabolomics approaches, we associated this pathway with the regulation of fatty acid (FA) metabolism. Moreover, we demonstrated that these signaling routes promote TNBC cell migration in vitro, suggesting they might be explored to identify potential therapeutic targets.

High Variability in Type and Indications for Bone Void Filler in Tibial Plateau Fracture Repair.

Tibial plateau fractures are a common injury treated by orthopaedic trauma surgeons. Depression of the articular surface of the tibial plateau is often an associated injury pattern. The methods used to address depressed tibial plateau fractures can vary, as it has yet to be determined if the type of bone void filler utilized affects the long-term functional outcomes of patients with tibial plateau fractures. A 28-question survey was created to better elucidate the current practices used by orthopaedic surgeons and the factors influencing the selection of bone void fillers for treatment of these injuries. The survey was distributed online to Orthopaedic Trauma Association (OTA) members. There were 106 orthopaedic surgeons that completed the survey with a wide range of responses. The survey determined the current practice of orthopaedic surgeons varies widely when selecting bone void fillers in the treatment of depressed tibial plateau fractures. (Journal of Surgical Orthopaedic Advances 32(3):156-159, 2023).

Disbiosis bacteriana y su efecto en enfermedades bucales: una revisión bibliográfica / Bacterial dysbiosis and its effect on oral diseases: a review bibliographic

Objetivo: actualizar la información sobre la disbiosis bacteriana oral y su efecto en enfermedades bucales. Material y métodos: se realizó una revisión bibliográfica detallada, donde la búsqueda de artículos comenzó desde el 2014 con trabajos de investigación relacionados con el tema. Se aplicaron palabras clave para facilitar y delimitar el tema. En los resultados obtenidos se observa información específica de disbiosis bacteriana y los problemas y enfermedades que causan en la cavidad bucal. Conclusión: la cavidad oral es un ecosistema muy complejo e interactivo donde se desarrollan variedades de hábitats que establecen relaciones entre los microorganismos en los distintos medios bucales. Por lo general, el cuerpo humano vive en simbiosis con dichas bacterias, esta relación hospedador-huésped es producto de años de evolución y convivencia para poder tolerar a dichas especies y por medio de años de investigación, determinar a los agentes patógenos y a los simbióticos, lo que permitirá en un futuro tener enfoques terapéuticos y científicos, para así solucionar, mejorar y evitar problemas relacionados con la salud (AU)

Objective: this review aimed to update the information on oral bacterial dysbiosis and its effect on oral diseases. Material and methods: a detailed literature review was performed, where the search for articles began in 2014 with research papers related to the topic. Keywords were applied to facilitate and delimit the topic. The results obtained show specific information on bacterial dysbiosis and the problems and diseases they cause in the oral cavity. Conclusion: the oral cavity is a very complex and interactive ecosystem where a variety of habitats develop and establish relationships between microorganisms in different oral environments. Generally, the human body lives in symbiosis with these bacteria, this host-guest relationship is the product of years of evolution and coexistence to be able to tolerate these species and through years of research to determine the pathogens and symbiotics, which will allow in the future to have therapeutic and scientific approaches, to solve, improve and avoid health-related problems (AU)

Nanomaterials-Based Combinatorial Therapy as a Strategy to Combat Antibiotic Resistance.

Since the discovery of antibiotics, humanity has been able to cope with the battle against bacterial infections. However, the inappropriate use of antibiotics, the lack of innovation in therapeutic agents, and other factors have allowed the emergence of new bacterial strains resistant to multiple antibiotic treatments, causing a crisis in the health sector. Furthermore, the World Health Organization has listed a series of pathogens (ESKAPE group) that have acquired new and varied resistance to different antibiotics families. Therefore, the scientific community has prioritized designing and developing novel treatments to combat these ESKAPE pathogens and other emergent multidrug-resistant bacteria. One of the solutions is the use of combinatorial therapies. Combinatorial therapies seek to enhance the effects of individual treatments at lower doses, bringing the advantage of being, in most cases, much less harmful to patients. Among the new developments in combinatorial therapies, nanomaterials have gained significant interest. Some of the most promising nanotherapeutics include polymers, inorganic nanoparticles, and antimicrobial peptides due to their bactericidal and nanocarrier properties. Therefore, this review focuses on discussing the state-of-the-art of the most significant advances and concludes with a perspective on the future developments of nanotherapeutic combinatorial treatments that target bacterial infections.

Evolution, Expression Patterns, and Distribution of Novel Ribbon Worm Predatory and Defensive Toxins.

Ribbon worms are active predators that use an eversible proboscis to inject venom into their prey and defend themselves with toxic epidermal secretions. Previous work on nemertean venom has largely focused on just a few species and has not investigated the different predatory and defensive secretions in detail. Consequently, our understanding of the composition and evolution of ribbon worm venoms is still very limited. Here, we present a comparative study of nemertean venom combining RNA-seq differential gene expression analyses of venom-producing tissues, tandem mass spectrometry-based proteomics of toxic secretions, and mass spectrometry imaging of proboscis sections, to shed light onto the composition and evolution of predatory and defensive toxic secretions in Antarctonemertes valida. Our analyses reveal a wide diversity of putative defensive and predatory toxins with tissue-specific gene expression patterns and restricted distributions to the mucus and proboscis proteomes respectively, suggesting that ribbon worms produce distinct toxin cocktails for predation and defense. Our results also highlight the presence of numerous lineage-specific toxins, indicating that venom evolution is highly divergent across nemerteans, producing toxin cocktails that might be finely tuned to subdue different prey. Our data also suggest that the hoplonemertean proboscis is a highly specialized predatory organ that seems to be involved in a variety of biological functions besides predation, including secretion and sensory perception. Overall, our results advance our knowledge into the diversity and evolution of nemertean venoms and highlight the importance of combining different types of data to characterize toxin composition in understudied venomous organisms.

Synthetic Biology Tools for Engineering Microbial Cells to Fight Superbugs.

With the increase in clinical cases of bacterial infections with multiple antibiotic resistance, the world has entered a health crisis. Overuse, inappropriate prescribing, and lack of innovation of antibiotics have contributed to the surge of microorganisms that can overcome traditional antimicrobial treatments. In 2017, the World Health Organization published a list of pathogenic bacteria, including Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Escherichia coli (ESKAPE). These bacteria can adapt to multiple antibiotics and transfer their resistance to other organisms; therefore, studies to find new therapeutic strategies are needed. One of these strategies is synthetic biology geared toward developing new antimicrobial therapies. Synthetic biology is founded on a solid and well-established theoretical framework that provides tools for conceptualizing, designing, and constructing synthetic biological systems. Recent developments in synthetic biology provide tools for engineering synthetic control systems in microbial cells. Applying protein engineering, DNA synthesis, and in silico design allows building metabolic pathways and biological circuits to control cellular behavior. Thus, synthetic biology advances have permitted the construction of communication systems between microorganisms where exogenous molecules can control specific population behaviors, induce intracellular signaling, and establish co-dependent networks of microorganisms.

Stability of the Microbiome of the Sponge Mycale (Oxymycale) acerata in the Western Antarctic Peninsula.

The sponge microbiome, especially in Low Microbial Abundance (LMA) species, is expected to be influenced by the local environment; however, contrasting results exist with evidence showing that host specificity is also important, hence suggesting that the microbiome is influenced by host-specific and environmental factors. Despite sponges being important members of Southern Ocean benthic communities, their relationships with the microbial communities they host remain poorly studied. Here, we studied the spatial and temporal patterns of the microbiota associated with the ecologically important LMA sponge M. acerata at sites along ∼400 km of the Western Antarctic Peninsula (WAP) to assess patterns in the core and variable microbial components of the symbiont communities of this sponge species. The analyses of 31 samples revealed that the microbiome of M. acerata is composed of 35 prokaryotic phyla (3 Archaea, 31 Bacteria, and one unaffiliated), being mainly dominated by Proteobacteria with Gammaproteobacteria as the most dominant class. The core community was composed of six prokaryotic OTUs, with gammaproteobacterial OTU (EC94 Family), showing a mean abundance over 65% of the total abundance. Despite some differences in rare OTUs, the core community did not show clear patterns in diversity and abundance associated with specific sites/environmental conditions, confirming a low variability in community structure of this species along the WAP. The analysis at small scale (Doumer Island, Palmer Archipelago) showed no differences in space and time in the microbiome M. acerata collected at sites around the island, sampled in three consecutive years (2016-2018). Our results highlight the existence of a low spatial and temporal variability in the microbiome of M. acerata, supporting previous suggestions based on limited studies on this and other Antarctic sponges.

Directly Reprogrammed Human Neurons to Understand Age-Related Energy Metabolism Impairment and Mitochondrial Dysfunction in Healthy Aging and Neurodegeneration.

Brain aging is characterized by several molecular and cellular changes grouped as the hallmarks or pillars of aging, including organelle dysfunction, metabolic and nutrition-sensor changes, stem cell attrition, and macromolecular damages. Separately and collectively, these features degrade the most critical neuronal function: transmission of information in the brain. It is widely accepted that aging is the leading risk factor contributing to the onset of the most prevalent pathological conditions that affect brain functions, such as Alzheimer's, Parkinson's, and Huntington's disease. One of the limitations in understanding the molecular mechanisms involved in those diseases is the lack of an appropriate cellular model that recapitulates the "aged" context in human neurons. The advent of the cellular reprogramming of somatic cells, i.e., dermal fibroblasts, to obtain directly induced neurons (iNs) and induced pluripotent stem cell- (iPSC-) derived neurons is technical sound advances that could open the avenues to understand better the contribution of aging toward neurodegeneration. In this review, we will summarize the commonalities and singularities of these two approaches for the study of brain aging, with an emphasis on the role of mitochondrial dysfunction and redox biology. We will address the evidence showing that iNs retain age-related features in contrast to iPSC-derived neurons that lose the aging signatures during the reprogramming to pluripotency, rendering iNs a powerful strategy to deepen our knowledge of the processes driving normal cellular function decline and neurodegeneration in a human adult model. We will finally discuss the potential utilization of these novel technologies to understand the differential contribution of genetic and epigenetic factors toward neuronal aging, to identify and develop new drugs and therapeutic strategies.

A phenolic-rich extract from Ugni molinae berries reduces abnormal protein aggregation in a cellular model of Huntington's disease.

Accumulation of misfolded proteins in the brain is a common hallmark of most age-related neurodegenerative diseases. Previous studies from our group identified the presence of anti-inflammatory and antioxidant compounds in leaves derived from the Chilean berry Ugni molinae (murtilla), in addition to show a potent anti-aggregation activity in models of Alzheimer´s disease. However, possible beneficial effects of berry extracts of murtilla was not investigated. Here we evaluated the efficacy of fruit extracts from different genotypes of Chilean-native U. molinae on reducing protein aggregation using cellular models of Huntington´s disease and assess the correlation with their chemical composition. Berry extraction was performed by exhaustive maceration with increasing-polarity solvents. An unbiased automatic microscopy platform was used for cytotoxicity and protein aggregation studies in HEK293 cells using polyglutamine-EGFP fusion proteins, followed by secondary validation using biochemical assays. Phenolic-rich extracts from murtilla berries of the 19-1 genotype (ETE 19-1) significantly reduced polyglutamine peptide aggregation levels, correlating with the modulation in the expression levels of autophagy-related proteins. Using LC-MS and molecular network analysis we correlated the presence of flavonoids, phenolic acids, and ellagitannins with the protective effects of ETE 19-1 effects on protein aggregation. Overall, our results indicate the presence of bioactive components in ethanolic extracts from U. molinae berries that reduce the load of protein aggregates in living cells.

Cdkn1a transcript variant 2 is a marker of aging and cellular senescence.

Cellular senescence is a cell fate response characterized by a permanent cell cycle arrest driven primarily the by cell cycle inhibitor and tumor suppressor proteins p16Ink4a and p21Cip1/Waf1. In mice, the p21Cip1/Waf1 encoding locus, Cdkn1a, is known to generate two transcripts that produce identical proteins, but one of these transcript variants is poorly characterized. We show that the Cdkn1a transcript variant 2, but not the better-studied variant 1, is selectively elevated during natural aging across multiple mouse tissues. Importantly, mouse cells induced to senescence in culture by genotoxic stress (ionizing radiation or doxorubicin) upregulated both transcripts, but with different temporal dynamics: variant 1 responded nearly immediately to genotoxic stress, whereas variant 2 increased much more slowly as cells acquired senescent characteristics. Upon treating mice systemically with doxorubicin, which induces widespread cellular senescence in vivo, variant 2 increased to a larger extent than variant 1. Variant 2 levels were also more sensitive to the senolytic drug ABT-263 in naturally aged mice. Thus, variant 2 is a novel and more sensitive marker than variant 1 or total p21Cip1/Waf1 protein for assessing the senescent cell burden and clearance in mice.

Scalable Total Synthesis, IP3R Inhibitory Activity of Desmethylxestospongin†B, and Effect on Mitochondrial Function and Cancer Cell Survival.

The scalable synthesis of the oxaquinolizidine marine natural product desmethylxestospongin B is based on the early application of Ireland-Claisen rearrangement, macrolactamization, and a late-stage installation of the oxaquinolizidine units by lactam reduction. The synthesis serves as the source of material to investigate calcium signaling and its effect on mitochondrial metabolism in various cell types, including cancer cells.

In the Right Place at the Right Time: Regulation of Cell Metabolism by IP3R-Mediated Inter-Organelle Ca2+ Fluxes.

In the last few years, metabolism has been shown to be controlled by cross-organelle communication. The relationship between the endoplasmic reticulum and mitochondria/lysosomes is the most studied; here, inositol 1,4,5-triphosphate (IP3) receptor (IP3R)-mediated calcium (Ca2+) release plays a central role. Recent evidence suggests that IP3R isoforms participate in synthesis and degradation pathways. This minireview will summarize the current findings in this area, emphasizing the critical role of Ca2+ communication on organelle function as well as catabolism and anabolism, particularly in cancer.