Cx43-mediated sorting of miRNAs into extracellular vesicles.

Through the exchange of lipids, proteins, and nucleic acids, extracellular vesicles (EV) allow for cell-cell communication across distant cells and tissues to regulate a wide range of physiological and pathological processes. Although some molecular mediators have been discovered, the mechanisms underlying the selective sorting of miRNAs into EV remain elusive. Previous studies demonstrated that connexin43 (Cx43) forms functional channels at the EV surface, mediating the communication with recipient cells. Here, we show that Cx43 participates in the selective sorting of miRNAs into EV through a process that can also involve RNA-binding proteins. We provide evidence that Cx43 can directly bind to specific miRNAs, namely those containing stable secondary structure elements, including miR-133b. Furthermore, Cx43 facilitates the delivery of EV-miRNAs into recipient cells. Phenotypically, we show that Cx43-mediated EV-miRNAs sorting modulates autophagy. Overall, our study ascribes another biological role to Cx43, that is, the selective incorporation of miRNAs into EV, which potentially modulates multiple biological processes in target cells and may have implications for human health and disease.

Integration of a tobacco cessation program into a rural community-based maternal and child health program in India: A stakeholders' perspective on task shifting.

INTRODUCTION: According to the Global Adult Tobacco Survey-2, India, 7.5% of pregnant women are tobacco users with a high prevalence of smokeless tobacco use in rural India. Although pregnant women may receive advice to quit tobacco, lack of knowledge on providing cessation support among healthcare workers results in missed opportunities. Community Health Workers (CHWs) play a significant role in maternal and child health (MCH) programs. Thus, task-shifting for providing cessation support by CHWs was planned and the perceptions and attitudes of concerned stakeholders were explored. METHOD: A pre-implementation qualitative study was conducted in four states of India within existing rural, community-based MCH program settings. Implementation research frameworks were used to develop data collection tools and for inductive and deductive thematic analysis. In-depth interviews were conducted with stakeholders (n=28) like coordinators, pregnant women and village functionaries of the government health system. Four focus groups were conducted with female CHWs (n=24). RESULTS: Stakeholders intended to adopt the intervention as objectives of the cessation intervention were aligned with the aims of the MCH program. CHWs related to their role in task-shifting and understood the context for implementing the intervention within the MCH program. Pregnant women expressed openness to receiving cessation support from CHWs acting as a facilitator for task-shifting. Barriers anticipated were the additional workload and time required for CHWs to implement the intervention. CONCLUSION: Task-shifting to female CHWs for screening tobacco users, providing brief advice and cessation support within the MCH program was perceived to be acceptable, adoptable and feasible. IMPLICATIONS: The study builds insight into the process of developing a grounded approach for the integration of tobacco cessation intervention into a rural, community-based antenatal care setting by task shifting to female community health workers for providing cessation support to pregnant women. The study fills gaps in the literature related to establishing tobacco cessation interventions for pregnant women. The delineated efforts in integration of the intervention and task shifting can be replicated in other developing countries, especially in rural communities within South Asian and Southeast Asian regions having cultural practices, community-based healthcare structures and tobacco consumption patterns that are comparable to India.

Effects of neonatal exposure to methoxychlor on corpus luteum in gilts: A transcriptomic analysis.

This study investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities, on luteal function in pigs. Piglets were injected subcutaneously with MXC (20 µg/kg body weight) or corn oil (control) between postnatal Days 1 and 10 (N = 5/group). Corpora lutea from sexually mature gilts were examined for luteal steroid and prostaglandin concentrations and processed for total RNA isolation and subsequent RNA sequencing. Intra-luteal concentrations of androstenedione and prostaglandin E2 were greater, while that of estrone was lower when compared to control. Fifty-three differentially expressed (DE) microRNAS (miRNAs) (p-adjusted <.05 and log2(fold change) ≥.5) and 359 DE genes (p-adjusted <.05 and log2(fold change) ≥1) were identified in luteal tissue in response to neonatal MXC treatment. MXC was found to affect the expression of genes related to lipogenesis, steroidogenesis, membrane transport, immune response, cell signaling and adhesion. These results suggest an earlier onset of structural luteolysis in pigs caused by MXC actions in neonates. Since negative correlation analysis showed the potential interactions of miRNAs with specific messenger RNAs, we propose that these miRNAs are potential mediators of the long-term MXC effect on the CL function in pigs.

Overlap between marine predators and proposed Marine Managed Areas on the Patagonian Shelf.

Static (fixed-boundary) protected areas are key ocean conservation strategies, and marine higher predator distribution data can play a leading role toward identifying areas for conservation action. The Falkland Islands are a globally significant site for colonial breeding marine higher predators (i.e., seabirds and pinnipeds). However, overlap between marine predators and Falkland Islands proposed Marine Managed Areas (MMAs) has not been quantified. Hence, to provide information required to make informed decisions regarding the implementation of proposed MMAs, our aims were to objectively assess how the proposed MMA network overlaps with contemporary estimates of marine predator distribution. We collated tracking data (1999-2019) and used a combination of kernel density estimation and model-based predictions of spatial usage to quantify overlap between colonial breeding marine predators and proposed Falkland Islands MMAs. We also identified potential IUCN Key Biodiversity Areas (pKBAs) using (1) kernel density based methods originally designed to identify Important Bird and Biodiversity Areas (IBAs) and (2) habitat preference models. The proposed inshore MMA, which extends three nautical miles from the Falkland Islands, overlapped extensively with areas used by colonial breeding marine predators. This reflects breeding colonies being distributed throughout the Falklands archipelago, and use being high adjacent to colonies due to central-place foraging constraints. Up to 45% of pKBAs identified via kernel density estimation were located within the proposed MMAs. In particular, the proposed Jason Islands Group MMA overlapped with pKBAs for three marine predator species, suggesting it is a KBA hot spot. However, tracking data coverage was incomplete, which biased pKBAs identified using kernel density methods, to colonies tracked. Moreover, delineation of pKBA boundaries were sensitive to the choice of smoothing parameter used in kernel density estimation. Delineation based on habitat model predictions for both sampled and unsampled colonies provided less biased estimates, and revealed 72% of the Falkland Islands Conservation Zone was likely a KBA. However, it may not be practical to consider such a large area for fixed-boundary management. In the context of wide-ranging marine predators, emerging approaches such as dynamic ocean management could complement static management frameworks such as MMAs, and provide protection at relevant spatiotemporal scales.

COVID-19 pandemic reduces the negative perception of oral health-related quality of life in adolescents.

PURPOSE: As people around the world are facing the Covid-19 outbreak, their perception of oral health problems could be changed. This study aimed to evaluate the immediate effects of the Covid-19 pandemic on oral health-related quality of life (OHRQoL) of adolescents. METHODS: A cohort study with schoolchildren from southern Brazil was conducted. Data on adolescents' OHRQoL were collected from December 2019 to February 2020 (T1), before the Brazilian Covid-19 outbreak. Posteriorly, the data were collected again in June and July of 2020 (T2), under the Brazilian Covid-19 outbreak. The OHRQoL was assessed using the Brazilian short version of the CPQ11-14. Demographic and socioeconomic characteristics and the degree of social distancing were also assessed. Changes in OHRQoL between T1 and T2 were evaluated by adjusted Multilevel Poisson regression models for repeated measures. RESULTS: From 290 individuals evaluated at T1, 207 were reevaluated at T2 (response rate of 71.3%). The overall CPQ11-14 mean score was significantly lower during the pandemic, reducing from 10.8 at T1 to 7.7 at T2. This significant reduction was also observed for all CPQ domains, indicating a lower negative impact of oral conditions on adolescents' quality of life during the pandemic. Adolescents from families that had a middle or low degree of social distancing during the pandemic and whose parents were harmed in employment had higher CPQ11-14 scores. CONCLUSION: Overall and specific-domains CPQ-14 scores were significantly lower during the Brazilian Covid-19 outbreak, indicating a decrease in the perception of oral health problems by adolescents over that period.

Effect of the COVID-19 pandemic on behavioural and psychosocial factors related to oral health in adolescents: A cohort study.

BACKGROUND: The impact of the COVID-19 pandemic on behavioural and psychosocial aspects related to oral health is unknown. AIM: This study evaluated the psychosocial and behavioural changes related to oral health in adolescents immediately before and during the pandemic period of COVID-19, enabling a longitudinal assessment of the perceived changes. DESIGN: This cohort study evaluated 290 adolescents from November 2019 to February 2020 (T1-before the pandemic in Brazil) and from June to July 2020 (T2) in southern Brazil. Sociodemographic, behavioural, and psychosocial variables were measured before and during the pandemic. Issues related to social distancing and job loss were also collected. The differences between the variables in T1 and T2, as well as the effect of social distancing, were assessed using a multilevel-adjusted logistic regression model for repeated measures. RESULTS: A total of 207 adolescents were re-evaluated at T2 (a response rate of 71.3%). During the pandemic, the frequency of toothbrushing, the use of dental services, and the self-perceived need for dental treatment significantly decreased. Sugar consumption, bruxism, and quality of sleep did not change significantly. CONCLUSION: Behavioural and psychosocial factors showed significant changes due to the COVID-19 pandemic in adolescents.

[Physical and emotional sequelae after hospitalization for COVID-19]. / Secuelas físicas y emocionales en pacientes post hospitalización por COVID-19.

BACKGROUND: Facing a severe life-threatening disease has physical and emotional consequences for patients. AIM: To evaluate the physical and emotional sequelae in patients who survived COVID-19 pneumonia. MATERIAL AND METHODS: This cross-sectional study collected data from post-COVID-19 pneumonia patients admitted to an outpatient follow-up program in a public hospital in Chile. One month after hospital discharge, the evaluation of physical capacity was carried out through the 1-minute sit-to-stand test (1STST). In addition, the Clinical Frailty Scale (CFS) and the Hospital Anxiety and Depression scale were applied. RESULTS: We included 70 patients aged 63 ± 13 years (54% women). Eighty-five percent of the patients were able to execute the 1STST with an average of 20.6 ± 4.8 repetitions. Forty-eight percent of the patients had a performance below the 2.5th percentile according to the reference values and 28% of patients had exertional desaturation. The CFS classified as mildly vulnerable or with some degree of frailty to 33% of patients. Twenty-five percent of the patients presented symptoms of depression and 33% of anxiety. CONCLUSIONS: Patients who survived COVID-19 have a decrease in physical capacity and a significant proportion of depression and anxiety one month after hospital discharge.

Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-α) in Stable Coronary Artery Disease.

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (ΔCt) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ΔCt miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.

Why do Adolescents Initiate and Continue Using Tobacco and Areca Nut?: A Qualitative Study Tracing Pathways of Use Among School-Going Adolescents in Mumbai, India.

BACKGROUND: Tobacco and areca-nut use among adolescents has been reported from different parts of India. Multiple factors influence initiation of tobacco use among adolescents. Initiation of one product gradually extends to multiple products. Studies on initiation lack documentation of the pathways and experiences post-initiation, which is required to holistically understand behavior patterns of adolescents for planning timely intervention. This study was conducted to trace pathways and identify factors influencing the initiation and continuation of tobacco and areca-nut among adolescents. METHODS: In this two-staged study, we conducted 14 focus group discussions (FGDs) with 166 adolescents studying in grades 7-9 (11-18 years) from six municipal schools in Mumbai, India. They had self-reported areca-nut or smoked or smokeless tobacco (SLT) use. Pathways of initiation were traced through in-depth interviews for 60 adolescents. RESULTS: Four multi-linear pathways of use were identified: (1) areca-nut only, (2) areca-nut to tobacco, (3) initiation with SLT, and (4) initiation with smoking. Raw or sweetened areca-nut, betel leaf, gutka, masheri, mawa, hookah, cigarette, bidi, and e-cigarettes were products reported to be used. Curiosity, easy access to tobacco products and normalization of tobacco use influenced initiation. Areca-nut acted as a precursor to tobacco use. CONCLUSION: Tracing pathways in tobacco use helped to understand reasons for initiation, influences in continuation of use, and experiences of significance to the adolescents. Experiences of adolescents play a critical role in shaping the pathways of tobacco use. Understanding the pathways and influencers will further help to build effective health promotion communication, policies for sale to minors, and school-based cessation interventions. IMPLICATIONS: Findings of the study provide an insight into unknown areas of information regarding products used by adolescents, their patterns of consumption, perceptions, and their pathways of initiation and continuation of primary and secondary products. This will help in developing specific public health awareness messages, policies regarding packaging and sale of areca-nut to children and interventions targeted for the adolescents and their specific products of use not just in India but for the South-East Asia region as areca-nut and tobacco use among adolescents is common in the region. The exercise of tracing the pathways provides basis for cessation counseling among adolescents.

Bioinformatics Research Methodology of Non-coding RNAs in Cardiovascular Diseases.

The transcriptional complexity generated by the human genomic output is within the core of cell and organ physiology, but also could be in the origin of pathologies. In cardiovascular diseases, the role of specific families of RNA transcripts belonging to the group of the non-coding RNAs started to be unveiled in the last two decades. The knowledge of the functional rules and roles of non-coding RNAs in the context of cardiovascular diseases is an important factor to derive new diagnostic methods, but also to design targeted therapeutic strategies. The characterization and analysis of ncRNA function requires a deep knowledge of the regulatory mechanism of these RNA species that often relies on intricated interaction networks. The use of specific bioinformatic tools to interrogate biological data and to derive functional implications is particularly relevant and needs to be extended to the general practice of translational researchers. This chapter briefly summarizes the bioinformatic tools and strategies that could be used for the characterization and functional analysis of non-coding RNAs, with special emphasis in their applications to the cardiovascular field.

Interactions Among Regulatory Non-coding RNAs Involved in Cardiovascular Diseases.

Non-coding RNAs (ncRNAs) are important regulatory players in human cells that have been shown to modulate different cellular processes and biological functions through controlling gene expression, being also involved in pathological conditions such as cardiovascular diseases. Among them, long non-coding RNAs (lncRNAs) and circular (circRNAs) could act as competing endogenous RNAs (ceRNAs) sequestering other ncRNAs. This entangled network of interactions has been reported to trigger the decay of the targeted ncRNAs having important roles in gene regulation. Growing evidences have been demonstrated that the regulatory mechanism underlying the crosstalk between different ncRNA species, namely lncRNAs, circRNAs and miRNAs has also an important role in the pathophysiological processes of cardiovascular diseases. In this chapter, the main regulatory relationship among lncRNAs, circRNAs and miRNAs were summarized and their role in the control and development of cardiovascular diseases was highlighted.

Fungal-host interactions: insights into microRNA in response to Paracoccidioides species.

BACKGROUND Paracoccidioides spp. causes paracoccidioidomycosis (PCM), an important and frequent systemic mycosis that occurs in Latin America. The infectious process begins with contact between the fungus and lung cells, and the molecular pattern of this interaction is currently poorly understood. MicroRNAs (miRNAs) are small non-coding RNAs that regulate the gene expression in many biological processes, including in the infections. OBJECTIVE This study aimed to analyse the expression of miRNAs in lung cells as response to infection by Paracoccidioides spp. METHODS A quantitative real-time polymerase chain reaction (RT-qPCR) based screening was employed to verify differentially expressed miRNAs in human lung cells infected with three different species; Paracoccidioides lutzii, Paracoccidioides americana, and Paracoccidioides brasiliensis. Furthermore, the in silico predictions of target genes and pathways for miRNAs were obtained. FINDINGS The results showed that miRNAs identified in the lung cells were different according to the species studied. However, based on the predicted targets, the potential signaling pathways regulated by miRNAs are common and related to adhesion, actin cytoskeleton rearrangement, apoptosis, and immune response mediated by T cells and TGF-ß. MAIN CONCLUSIONS In summary, this study showed the miRNAs pattern of epithelial cells in response to infection by Paracoccidioides species and the potential role of these molecules in the regulation of key pathogenesis mechanisms of PCM.

Interspecies Communication in Holobionts by Non-Coding RNA Exchange.

Complex organisms are associations of different cells that coexist and collaborate creating a living consortium, the holobiont. The relationships between the holobiont members are essential for proper homeostasis of the organisms, and they are founded on the establishment of complex inter-connections between all the cells. Non-coding RNAs are regulatory molecules that can also act as communication signals between cells, being involved in either homeostasis or dysbiosis of the holobionts. Eukaryotic and prokaryotic cells can transmit signals via non-coding RNAs while using specific extracellular conveyors that travel to the target cell and can be translated into a regulatory response by dedicated molecular machinery. Within holobionts, non-coding RNA regulatory signaling is involved in symbiotic and pathogenic relationships among the cells. This review analyzes current knowledge regarding the role of non-coding RNAs in cell-to-cell communication, with a special focus on the signaling between cells in multi-organism consortia.

Circular RNA-Centered Regulatory Networks in the Physiopathology of Cardiovascular Diseases.

Non-coding regulatory RNAs are generated as a core output of the eukaryotic genomes, being essential players in cell biology. At the organism level, they are key functional actors in those tissues and organs with limited proliferation capabilities such as the heart. The role of regulatory networks mediated by non-coding RNAs in the pathophysiology of cardiovascular conditions is starting to be unveiled. However, a deeper knowledge of the functional interactions among the diverse non-coding RNA families and their phenotypic consequences is required. This review presents the current knowledge about the functional crosstalk between circRNAs and other biomolecules in the framework of the cardiovascular diseases.

Design, Synthesis, and In Vitro Evaluation of Hydroxybenzimidazole-Donepezil Analogues as Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease.

A series of multi-target-directed ligands (MTDLs), obtained by attachment of a hydroxyphenylbenzimidazole (BIM) unit to donepezil (DNP) active mimetic moiety (benzyl-piperidine/-piperazine) was designed, synthesized, and evaluated as potential anti-Alzheimer's disease (AD) drugs in terms of biological activity (inhibition of acetylcholinesterase (AChE) and ß-amyloid (Aß) aggregation), metal chelation, and neuroprotection capacity. Among the DNP-BIM hybrids studied herein, the structural isomerization did not significantly improve the biological properties, while some substitutions, namely fluorine atom in each moiety or the methoxy group in the benzyl ring, evidenced higher cholinergic AChE activity. All the compounds are able to chelate Cu and Zn metal ions through their bidentate BIM moieties, but compound 5, containing a three-dentate chelating unit, is the strongest Cu(II) chelator. Concerning the viability on neuroblastoma cells, compounds 9 and 10 displayed the highest reduction of Aß-induced cell toxicity. In silico calculations of some pharmacokinetic descriptors indicate that all the compounds but the nitro derivatives have good potential oral-bioavailability. Overall, it can be concluded that most of the studied DNP-BIM conjugates showed quite good anti-AD properties, therefore deserving to be considered in further studies with the aim of understanding and treating AD.

Development of Chlorhexidine Digluconate and Lippia sidoides Essential Oil Loaded in Microemulsion for Disinfection of Dental Root Canals: Substantivity Profile and Antimicrobial Activity.

The dental intracanal disinfection is crucial to achieve the success of endodontic treatment, avoiding the maintenance of endodontic infections. Chlorhexidine digluconate can act as an irrigating agent for it. However, it can cause tissue irritation in high concentrations. Therefore, combinations with other antimicrobial agents and more efficient therapeutic alternatives are studied, which make it possible to administer drugs more safely and with minimal adverse effects. Thus, the objective of this study was the development of a microemulsion containing chlorhexidine digluconate and essential oil of Lippia sidoides to be used for disinfection of dental root canals and to evaluate its profile of substantivity and antimicrobial activity. The microemulsions were obtained through phase diagrams, using the spontaneous formation method. We completed a physical-chemical characterization and evaluate the stability of the microemulsions, in addition to the substantivity profile in a bovine root dentin model, and in vitro antibacterial effect on Enterococcus faecalis. A method for quantifying chlorhexidine was developed using UV-Vis spectroscopy. The microemulsions showed acid pH, conductivity above 1.3 µScm-1, and dispersion index similar to water. The microemulsions showed antimicrobial inhibition halos similar to the commercial gel conventionally used, but with four times more substantivity to dentinal tissues. Microemulsions were obtained as a therapeutic alternative to formulations available on the market, presenting themselves as a system with great potential for the administration of drugs for disinfection of root canals.

The circulating non-coding RNA landscape for biomarker research: lessons and prospects from cardiovascular diseases.

Pervasive transcription of the human genome is responsible for the production of a myriad of non-coding RNA molecules (ncRNAs) some of them with regulatory functions. The pivotal role of ncRNAs in cardiovascular biology has been unveiled in the last decade, starting from the characterization of the involvement of micro-RNAs in cardiovascular development and function, and followed by the use of circulating ncRNAs as biomarkers of cardiovascular diseases. The human non-coding secretome is composed by several RNA species that circulate in body fluids and could be used as biomarkers for diagnosis and outcome prediction. In cardiovascular diseases, secreted ncRNAs have been described as biomarkers of several conditions including myocardial infarction, cardiac failure, and atrial fibrillation. Among circulating ncRNAs, micro-RNAs (miRNAs), long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have been proposed as biomarkers in different cardiovascular diseases. In comparison with standard biomarkers, the biochemical nature of ncRNAs offers better stability and flexible storage conditions of the samples, and increased sensitivity and specificity. In this review we describe the current trends and future prospects of the use of the ncRNA secretome components as biomarkers of cardiovascular diseases, including the opening questions related with their secretion mechanisms and regulatory actions.

Popliteal vein aneurysm: report of two cases.

Venous aneurysms are rare and often diagnosed incidentally. Popliteal vein aneurysms are the most common type of venous aneurysms and have a strong association with the occurrence of deep vein thrombosis and recurrent pulmonary embolism. This article reports two cases of popliteal vein aneurysms associated with deep vein thrombosis.

Characterization of the kefir beverage produced from yam (Colocasia esculenta L.), sesame seed (Sesamum indicum L.) and bean (Phaseolus vulgaris L.) extracts.

The objective of this study was to evaluate the characteristics of kefir beverages made from yam, sesame and bean extracts after fermentation of the extracts with water kefir grains. Formulations were prepared with raw and boiled yams. To the yam extract, sesame and different percentages of white bean extract were added. The fermentation kinetics, the chemical composition and color of the extracts were analyzed. To determine the fermentation kinetic parameters, pH and titratable acidity were evaluated. The chemical composition and color of all extracts were determined before and after fermentation process. The decrease in pH and increase in titratable acidity were affected both by raw or boiler yam. The addition of bean extract favored the decrease in pH of formulations containing extracts of raw or boiled yams. Chemical composition and color of the beverages were altered after fermentation. The kefir beverage made from yam and sesame enriched with 50% beans proved to be an excellent fermentation substrate. In addition, it is a new way of consuming vegetable products, especially fermented products, which have limited diversity to serve vegan consumers and also people with certain allergies to dairy products.

Noncoding Transcriptional Landscape in Human Aging.

Aging is a universal phenomenon in metazoans, characterized by a general decline of the organism physiology associated with an increased risk of mortality and morbidity. Aging of an organism correlates with a decline in function of its cells, as shown for muscle, immune, and neuronal cells. As the DNA content of most cells within an organism remains largely identical throughout the life span, age-associated transcriptional changes must be achieved by epigenetic mechanisms. However, how aging may impact on the epigenetic state of cells is only beginning to be understood. In light of a growing number of studies demonstrating that noncoding RNAs can provide molecular signals that regulate expression of protein-coding genes and define epigenetic states of cells, we hypothesize that noncoding RNAs could play a direct role in inducing age-associated profiles of gene expression. In this context, the role of long noncoding RNAs (lncRNAs) as regulators of gene expression might be important for the overall transcriptional landscape observed in aged human cells. The possible functions of lncRNAs and other noncoding RNAs, and their roles in the regulation of aging-related cellular pathways will be analyzed.