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Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer. Significance: LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.

LDL-exposed breast cancer cells show differential invasion potential and metastatic tropism to distant sites in xenotransplanted zebrafish larvae at 4dpi (6dpf). Related to Fig. 1.

List of primers used for measurements of gene expression levels and mtDNA content by quantitative real-time PCR.

Most cancer-related deaths are due to metastases. Systemic factors, such as lipid-enriched environments [as low-density lipoprotein (LDL)-cholesterol], favor breast cancer, including triple-negative breast cancer (TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL increases lipid droplets, induces CD36 and augments TNBC cells migration and invasion in vivo and in vitro. LDL induces higher mitochondrial mass and network spread in migrating cells, in an actin remodeling-dependent manner, and transcriptomic and energetic analyses revealed that LDL renders TNBC cells dependent on fatty acids (FA) usage for mitochondrial respiration. Indeed, engagement on FA transport into the mitochondria is required for LDL-induced migration and mitochondrial remodeling. Mechanistically, LDL treatment leads to mitochondrial long-chain fatty acid accumulation and increased reactive oxygen species (ROS) production. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer.Significance:LDL induces breast cancer cell migration that relies on CD36 for mitochondrial metabolism and network remodeling, providing an antimetastatic metabolic strategy.

Endothelial dysfunction has been suggested as a potential mechanism contributing to the development and progression of heart failure (HF). Levels of circulating endothelial cells (CECs), endothelial progenitor cells (EPCs), and hematopoietic stem and progenitor cells (HSPCs) have been recognized as useful markers of vascular damage and endothelial repair in response to tissue injury.To evaluate the circulating levels of EPCs, CECs, and HSPCs among patients with HF with reduced ejection fraction (HFrEF).In 82 individuals (42 patients with HFrEF and 42 age-matched subjects without established cardiovascular disease), peripheral blood was drawn and levels of EPCs, CECs, and HSPCs were quantified by flow cytometry.Patients with HFrEF showed lower levels of circulating EPCs (5.28 × 10Circulating levels of EPCs and CECs were significantly decreased in patients with HFrEF in comparison to age-matched subjects without established cardiovascular disease, suggesting that the levels of CECs and EPCs may be potential biomarkers of the cellular response to vascular injury in patients with HFrEF.

Most cancer related deaths are due to metastases. Systemic factors, such as lipid-enriched environments (particularly LDL-cholesterol), favor breast cancer (including triple negative breast cancer, TNBC) metastasis formation. Mitochondria metabolism impacts TNBC invasive behavior but its involvement in a lipid-enriched setting is undisclosed. Here we show that LDL-cholesterol induces CD36, increases lipid droplets and augments TNBC cells migration and invasion in vivo and in vitro. LDL increases mitochondrial mass and mitochondria spread in migrating cells, and energetic analyses revealed that LDL renders TNBC dependent on fatty acids for mitochondrial respiration. Indeed, engagement of fatty acid oxidation, but not glycolysis, is required for LDL-induced migration and mitochondrial remodeling. Moreover, LDL induced reactive oxygen species (ROS) production by TNBC cells. Importantly, CD36 or ROS blockade abolished LDL-induced cell migration and mitochondria metabolic adaptations. Our data suggest that LDL induces TNBC cells migration by reprogramming mitochondrial metabolism, revealing a new vulnerability in metastatic breast cancer.

© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated., Background: Long non-coding RNAs (lncRNAs) represent a substantial portion of the human transcriptome. LncRNAs present a very stringent cell-type/tissue specificity being potential candidates for therapeutical applications during aging and disease. As example, targeting of MALAT1, a highly conserved lncRNA originally identified in metastatic non-small cell lung cancer, has shown promising results in cancer regression. Nevertheless, the regulation and specificity of MALAT1 have not been directly addressed. Interestingly, MALAT1 locus is spanned by an antisense transcript named TALAM1. Methods: Here using a collection of breast cancer cells and in vitro and in vivo migration assays we characterized the dynamics of expression and demonstrated that TALAM1 regulates and synergizes with MALAT1 during tumorigenesis. Results: Down-regulation of TALAM1 was shown to greatly impact on the capacity of breast cancer cells to migrate in vitro or to populate the lungs of immunocompromised mice. Additionally, we demonstrated that TALAM1 cooperates with MALAT1 in the regulation of the properties guiding breast cancer aggressiveness and malignancy. Conclusions: By characterizing this sense/anti-sense pair we uncovered the complexity of MALAT1 locus regulation, describing new potential candidates for cancer targeting., This work was supported by Fundação para a Ciência e Tecnologia (FCT) (PTDC/BIM-MED/0032/2014); UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/ Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado; LISBOA-01-0145-FEDER-016394, projeto cofinanciado pelo FEDER através POR Lisboa 2020 - Programa Operacional Regional de Lisboa, do PORTUGAL 2020 e pela Fundação para a Ciência e a Tecnologia; LISBOA-01-0145-FEDER-028534, projeto cofinanciado pelo FEDER através POR Lisboa 2020 - Programa Operacional Regional de Lisboa, do PORTUGAL 2020 e pela Fundação para a Ciência e a Tecnologia. B.B.J. was an FCT Investigator (IF/00166/2014). C.V. was a Gulbenkian Foundation Fellow. S.N.-P. was recipient of an individual FCT postdoctoral fellowship (SFRH/BPD/91159/2012).

Heart disease is the leading cause of mortality in developed countries. The associated pathology is typically characterized by the loss of cardiomyocytes that leads, eventually, to heart failure. Although conventional treatments exist, novel regenerative procedures are warranted for improving cardiac regeneration and patients well fare. Whereas following injury the capacity for regeneration of adult mammalian heart is limited, the neonatal heart is capable of substantial regeneration but this capacity is lost at postnatal stages. Interestingly, this is accompanied by a shift in the metabolic pathways and energetic fuels preferentially used by cardiomyocytes from embryonic glucose-driven anaerobic glycolysis to adult oxidation of substrates in the mitochondria. Apart from energetic sources, metabolites are emerging as key regulators of gene expression and epigenetic programs which could impact cardiac regeneration. Long non-coding RNAs (lncRNAs) are known master regulators of cellular and organismal carbohydrate and lipid metabolism and play multifaceted functions in the cardiovascular system. Still, our understanding of the metabolic determinants and pathways that can promote cardiac regeneration in the injured hearth remains limited. Here, we will discuss the emerging concepts that provide evidence for a molecular interplay between lncRNAs and metabolic signaling in cardiovascular function and whether exploiting this axis could provide ground for improved regenerative strategies in the heart.

Copyright © 2021 Santos, Correia, Nóbrega-Pereira and Bernardes de Jesus. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms., Aging imposes a barrier for tissue regeneration. In the heart, aging leads to a severe rearrangement of the cardiac structure and function and to a subsequent increased risk of heart failure. An intricate network of distinct pathways contributes to age-related alterations during healthy heart aging and account for a higher susceptibility of heart disease. Our understanding of the systemic aging process has already led to the design of anti-aging strategies or to the adoption of protective interventions. Nevertheless, our understanding of the molecular determinants operating during cardiac aging or repair remains limited. Here, we will summarize the molecular and physiological alterations that occur during aging of the heart, highlighting the potential role for long non-coding RNAs (lncRNAs) as novel and valuable targets in cardiac regeneration/repair., This work was supported by Fundação para a Ciência e Tecnologia (FCT; ERA-CVD 2018 / 3599-PPCDT - ERA-CVD/0001/2018 - INNOVATION).

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)., Despite improvements in cancer therapy, metastatic solid tumors remain largely incurable. Immunotherapy has emerged as a pioneering and promising approach for cancer therapy and management, and in particular intended for advanced tumors unresponsive to current therapeutics. In cancer immunotherapy, components of the immune system are exploited to eliminate cancer cells and treat patients. The recent clinical successes of immune checkpoint blockade and chimeric antigen receptor T cell therapies represent a turning point in cancer treatment. Despite their potential success, current approaches depend on efficient tumor antigen presentation which are often inaccessible, and most tumors turn refractory to current immunotherapy. Patient-derived induced pluripotent stem cells (iPSCs) have been shown to share several characteristics with cancer (stem) cells (CSCs), eliciting a specific anti-tumoral response when injected in rodent cancer models. Indeed, artificial cellular reprogramming has been widely compared to the biogenesis of CSCs. Here, we will discuss the state-of-the-art on the potential implication of cellular reprogramming and iPSCs for the design of patient-specific immunotherapeutic strategies, debating the similarities between iPSCs and cancer cells and introducing potential strategies that could enhance the efficiency and therapeutic potential of iPSCs-based cancer vaccines., This research was funded by Fundação para a Ciência e Tecnologia (FCT), and FEDER, LISBOA-01-0145-FEDER-028534, project co-funded by FEDER, through POR Lisboa 2020—Programa Operacional Regional de Lisboa, PORTUGAL 2020, FEDER—Fundo Europeu de Desenvolvimento Regional through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020, by Portuguese funds through FCT, in the framework of the project UIDB/04501/2020 to iBiMED and by the European Commission (ERA-CVD Joint Call 2018, grant#INNOVATION) through FCT and the Portuguese Ministry of Health, through the Directorate General of Health (DGS).

In this chapter, we will discuss how aging impacts the dynamics of stem cells and affects cellular reprogramming. We will discuss certain pathways involved in the aging process, and how we can use those pathways to increase the efficiency of the reprogramming protocol. Furthermore, we will describe two protocols to establish primary cultures of a “young” cell line (mouse embryonic fibroblasts—MEFs) and an adult/old cell line (primary cultures of adult/old mouse ear fibroblasts). These cell lines are often the primary choice to study aging in vitro.

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/)., Epithelial⁻mesenchymal transition (EMT) is a cellular process by which differentiated epithelial cells undergo a phenotypic conversion to a mesenchymal nature. The EMT has been increasingly recognized as an essential process for tissue fibrogenesis during disease and normal aging. Higher levels of EMT proteins in aged tissues support the involvement of EMT as a possible cause and/or consequence of the aging process. Here, we will highlight the existing understanding of EMT supporting the phenotypical alterations that occur during normal aging or pathogenesis, covering the impact of EMT deregulation in tissue homeostasis and stem cell function., This work was supported by Fundação para a Ciência e Tecnologia (FCT) (PTDC/BIM-MED/0032/2014). S.N.-P. has a FCT contract.

One of the most outstanding observations from next‐generation sequencing approaches was that only 1.5% of our genes code for proteins. The biggest part is transcribed but give rise to different families of RNAs without coding potential. The functional relevance of these abundant transcripts remains far from elucidated. Among them are the long non‐coding RNAs (lncRNAs), a relatively large and heterogeneous group of RNAs shown to be highly tissue‐specific, indicating a prominent role in processes controlling cellular identity. In particular, lncRNAs have been linked to both stemness properties and detrimental pathways regulating the aging process, being novel players in the intricate network guiding tissue homeostasis. Here, we summarize the up‐to‐date information on the role of lncRNAs that affect stemness and hence impact upon aging, highlighting the likelihood that lncRNAs may represent an unexploited reservoir of potential therapeutic targets for reprogramming applications and aging‐related diseases.

Random binary matrices appear in a variety of signal processing and encoding problems. They play an important role in rateless codes and in distributed storage applications. This paper focuses on block angular matrices, a class of random rectangular binary matrices that are particularly suited to distributed storage applications. We address one of the key issues regarding binary random matrices in general, and block angular matrices in particular: the probability of obtaining a full rank matrix, when drawing uniformly at random from the set of binary matrices with compatible structure. This paper gives a closed-form expression for this probability, as well as some bounds and approximations.

SummaryAberrantly short telomeres result in decreased longevity in both humans and mice with defective telomere maintenance. Normal populations of humans and mice present high interindividual variation in telomere length, but it is unknown whether this is associated with their lifespan potential. To address this issue, we performed a longitudinal telomere length study along the lifespan of wild-type and transgenic telomerase reverse transcriptase mice. We found that mouse telomeres shorten ∼100 times faster than human telomeres. Importantly, the rate of increase in the percentage of short telomeres, rather than the rate of telomere shortening per month, was a significant predictor of lifespan in both mouse cohorts, and those individuals who showed a higher rate of increase in the percentage of short telomeres were also the ones with a shorter lifespan. These findings demonstrate that short telomeres have a direct impact on longevity in mammals, and they highlight the importance of performing longitudinal telomere studies to predict longevity.

A major goal in cancer and aging research is to discriminate the biochemical modifications that happen locally that could account for the healthiness or malignancy of tissues. Senescence is one general antiproliferative cellular process that acts as a strong barrier for cancer progression, playing a crucial role in aging. Here, we focus on the current methods to assess cellular senescence, discriminating the advantages and disadvantages of several senescence biomarkers.

A major goal in aging research is to improve health during aging. In the case of mice, genetic manipulations that shorten or lengthen telomeres result, respectively, in decreased or increased longevity. Based on this, we have tested the effects of a telomerase gene therapy in adult (1 year of age) and old (2 years of age) mice. Treatment of 1- and 2-year old mice with an adeno associated virus (AAV) of wide tropism expressing mouse TERT had remarkable beneficial effects on health and fitness, including insulin sensitivity, osteoporosis, neuromuscular coordination and several molecular biomarkers of aging. Importantly, telomerase-treated mice did not develop more cancer than their control littermates, suggesting that the known tumorigenic activity of telomerase is severely decreased when expressed in adult or old organisms using AAV vectors. Finally, telomerase-treated mice, both at 1-year and at 2-year of age, had an increase in median lifespan of 24 and 13%, respectively. These beneficial effects were not observed with a catalytically inactive TERT, demonstrating that they require telomerase activity. Together, these results constitute a proof-of-principle of a role of TERT in delaying physiological aging and extending longevity in normal mice through a telomerase-based treatment, and demonstrate the feasibility of anti-aging gene therapy.

Summary Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc + ⁄ ) MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc ) ⁄ ) littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.

Sewage sludge use in agriculture should be limited by the presence of metals and other persistent environmental pollutants. The present study aims to contribute for the definition of a test battery of ecotoxicological assays that allows a proper ecotoxicological characterization of sludges, providing information on their potential hazard and identified “safe” application levels. Three sludges from distinct sources (urban, olive-processing, and electroplating industries) were tested using avoidance and reproduction tests with earthworms (Eisenia andrei) and springtails (Folsomia candida) and plant growth tests with turnips (Brassica rapa) and oats (Avena sativa). Different soil–sludge mixture concentrations mimicking recommended/realistic field dosages were tested. Only the sludge from the electroplating industry induced an avoidance response from the earthworms (EC50 = 0.4 t/ha) and collembolans (no observed effect concentration (NOEC) = 15 t/ha). This sludge was the only sludge responsible for any effect on the reproductive output of the earthworms (EC50 = 7.74 t/ha). Regarding collembolans, none of the sludges tested caused any significant decrease in reproduction. In higher plant tests, the two industrial sludges were toxic, causing a decrease growth in both species. The EC20 values determined for B. rapa were 20.3 and 24.2 t/ha and for A. sativa 14.7 and 16.2 t/ha for sludges from olive-processing and electroplating industries, respectively. The metal loadings of the different test sludges could partially explain the results obtained. The toxicity of the test sludge from electroplating industry observed on the tested invertebrates and plants could be explained by the high amount of total chromium from which 22.3% was in the most toxic oxidation state—Cr(VI). However, the toxicity caused by the sludge from the olive-processing industry in the test plants could be attributed to the presence of other compounds (not measured in this study) since the metal content was not high enough to induce such an effect. The absence of toxicity showed by the urban test sludge was in agreement with its low levels of metals. The response of the different test organisms and end points varied according to the sludge type. The urban sludge was non-toxic whereas the sludge from the electroplating industry caused a toxic effect on almost all parameters measured (avoidance behavior of both test organisms, reproduction of earthworms, and growth of both plant species). Sludge from the olive-processing industry only caused a toxic effect on growth of both plant species. By analyzing the sensitivity of the different parameters for the most toxic sludge, it was found that avoidance and reproduction were more sensitive than plant growth, whereas plant seed germination was not sensitive at all. The ecotoxicological evaluation of wastes can be used as an environmental safety control of sludge use in agriculture. A tiered approach could be adopted for this purpose, incorporating avoidance tests in the first tier (screening level) and reproduction and plant growth tests in a second tier. But more evidence aiming to define the most suitable ecotoxicological test battery for specific sludges with a different contamination profile is still needed.

Coronary heart disease is one of the main causes of death in the developed world, and treatment success remains modest, with high mortality rates within 1 year after myocardial infarction (MI). Thus, new therapeutic targets and effective treatments are necessary. Short telomeres are risk factors for age-associated diseases, including heart disease. Here we address the potential of telomerase (Tert) activation in prevention of heart failure after MI in adult mice. We use adeno-associated viruses for cardiac-specific Tert expression. We find that upon MI, hearts expressing Tert show attenuated cardiac dilation, improved ventricular function and smaller infarct scars concomitant with increased mouse survival by 17% compared with controls. Furthermore, Tert treatment results in elongated telomeres, increased numbers of Ki67 and pH3-positive cardiomyocytes and a gene expression switch towards a regeneration signature of neonatal mice. Our work suggests telomerase activation could be a therapeutic strategy to prevent heart failure after MI.

Although cancer and aging have been studied as independent diseases, mounting evidence suggest that cancer is an aging-associated disease and that cancer and aging share many molecular pathways. In particular, recent studies validated telomerase activation as a potential therapeutic target for age-related diseases, and at the same time, abnormal telomerase expression and telomerase mutations have been associated with many different types of human tumors. Here, we revisit the connection of telomerase to cancer and aging in light of recent findings supporting a role for telomerase not only in telomere elongation, but also in metabolic fitness and Wnt activation. Understanding the physiological impact of telomerase regulation is fundamental considering the therapeutic strategies that are being developed involving telomerase modulation.

Our understanding of the mechanisms by which aging is produced is still very limited. Here, we have determined the sera metabolite profile of 117 wild-type mice of different genetic backgrounds ranging from 8 to 129 weeks of age. This has allowed us to define a robust metabolomic signature and a derived metabolomic score that reliably/accurately predicts the age of wild-type mice. In the case of telomerase-deficient mice, which have a shortened lifespan, their metabolomic score predicts older ages than expected. Conversely, in the case of mice that overexpress telomerase, their metabolic score corresponded to younger ages than expected. Importantly, telomerase reactivation late in life by using a TERT-based gene therapy recently described by us significantly reverted the metabolic profile of old mice to that of younger mice, further confirming an anti-aging role for telomerase. Thus, the metabolomic signature associated with natural mouse aging accurately predicts aging produced by telomere shortening, suggesting that natural mouse aging is in part produced by presence of short telomeres. These results indicate that the metabolomic signature is associated with the biological age rather than with the chronological age. This constitutes one of the first aging-associated metabolomic signatures in a mammalian organism.

Caloric restriction (CR), a reduction of food intake while avoiding malnutrition, can delay the onset of cancer and age-related diseases in several species, including mice. In addition, depending of the genetic background, CR can also increase or decrease mouse longevity. This has highlighted the importance of identifying the molecular pathways that interplay with CR in modulating longevity. Significant lifespan extension in mice has been recently achieved through over-expression of the catalytic subunit of mouse telomerase (mTERT) in a cancer protective background. Given the CR cancer-protective effects in rodents, we set to address here whether CR impacts on telomere length and synergizes with mTERT to extend mouse longevity. CR significantly decreased tumor incidence in TERT transgenic (TgTERT) mice and extended their lifespan compared to wild-type (WT) controls under the same diet, indicating a synergy between TgTERT and CR in increasing mouse longevity. In addition, longitudinal telomere length measurements in peripheral blood leukocytes from individual mice showed that CR resulted in maintenance and/or elongation telomeres in a percentage of WT mice, a situation that mimics telomere dynamics in TgTERT cohorts. These results demonstrate that CR attenuates telomere erosion associated to aging and that synergizes with TERT over-expression in increasing “health span” and extending mouse longevity.

The progressive increase in the elderly population worldwide has resulted in higher numbers of individuals affected by age-associated diseases, such as neurodegenerative and heart diseases, metabolic impairment, or cancer, with the subsequent burden for national health systems. Therapeutic interventions aimed to increase the quality of life at advanced age are visualized as important demands for the future, both at the level of individuals and society. Novel advances in telomerase function from several independent laboratories have resulted in potential new therapeutic strategies which appear as promising new venues to prevent cellular and tissue dysfunction and organismal decline, thereby increasing the so-called “health span”. Here, we analyze these recent advances.

Random binary matrices have found many applications in signal processing and coding. Rateless codes, for example, are based on the random generation of codewords by means of inner products between the data and random binary vectors. But the usefulness of random binary matrices is not limited to coding: they are also well suited to distributed data storage applications. In this context, random binary matrices with block-angular structure are of particular interest because they allow cooperative encoding and decentralized models for coding and decoding, with a built-in degree of parallelism. Linear programming, LUfactorization andQRfactorization are some of the problems for which the coarse-grain parallelization inherent in the block-angular structure is of interest. This paper studies one of the most important characteristics of block-angular matrices, their rank. More precisely, we study the rank distribution and full rank probability of rectangular random binary matrices and block-angular matrices in GF(2).

Here, we show that a small-molecule activator of telomerase (TA-65) purified from the root of Astragalus membranaceus is capable of increasing average telomere length and decreasing the percentage of critically short telomeres and of DNA damage in haploinsufficient mouse embryonic fibroblasts (MEFs) that harbor critically short telomeres and a single copy of the telomerase RNA Terc gene (G3 Terc(+/-) MEFs). Importantly, TA-65 does not cause telomere elongation or rescue DNA damage in similarly treated telomerase-deficient G3 Terc(-/-) littermate MEFs. These results indicate that TA-65 treatment results in telomerase-dependent elongation of short telomeres and rescue of associated DNA damage, thus demonstrating that TA-65 mechanism of action is through the telomerase pathway. In addition, we demonstrate that TA-65 is capable of increasing mouse telomerase reverse transcriptase levels in some mouse tissues and elongating critically short telomeres when supplemented as part of a standard diet in mice. Finally, TA-65 dietary supplementation in female mice leads to an improvement of certain health-span indicators including glucose tolerance, osteoporosis and skin fitness, without significantly increasing global cancer incidence.

In this work we show that coding with a binary block angular matrix with some extra coupling rows can achieve similar results to codes that use other random binary matrices. Moreover, we also show that it is possible to use sparse block diagonal matrices and get the same results obtained with a dense equiprobable binary random matrix. The block diagonal form of the matrix grants an inherent parallelism for the decoding process. This characteristics can be used to speedup the decoding process with multicore architectures while reducing the communication between the cores. On storage applications it would be possible to perform the reconstruction of local data while minimizing the communication.

The basic theories of compressed sensing (CS) turn around the sampling and reconstruction of 1-D signals. To deal with 2-D signals (images), the conventional treatment is to convert them into1-D vectors. This has drawbacks, including huge memory demands and difficulties in the design and calibration of the optical imaging systems. As a result, in 2009 some researchers proposed the concept of compressed imaging (CI) with separable sensing operators. However, their work is only focused on the sampling phase. In this paper, we propose a scheme for 2-D CS that is memory- and computation-efficient in both sampling and reconstruction. This is achieved by decomposing the 2-D CS problem into two stages with the help of an intermediate image. The intermediate image is then solved by direct orthogonal linear transform and the original image is reconstructed by solving a set of 1-D l1-norm minimization sub-problems. The experimental results confirm the feasibility of the proposed scheme.

Batch algorithms of matching pursuit (MP) and orthogonal matching pursuit (OMP) are proposed in this paper. In both algorithms, the original iteration procedures are modified in the following way. Instead of finding a single best-matched atom in each iteration, we find a number of best-matched atoms to speed up the convergence, - a batch version. Then optimized coefficients are computed based on these atoms. Numerical simulations in the application to compressed sensing show that the proposed algorithms are much faster than the original ones, while similar reconstruction precision is obtained.

Rateless codes for erasure channels were recently proposed by Luby with very efficient coding and decoding schemes. However, designing an efficient decoding rateless code for Binary Error Channel (BEC), still remains a difficult problem. In this work we propose a rateless decoding algorithm for the BEC using a coding matrix G with a high level of sparsity. The distribution used to generate the elements of G can be designed to give with high probability a sub-matrix B of G with a sparse inverse leading to an efficient way of computing the syndrome. We show that our method is able to update the syndrome from a previous evaluation. However to obtain the error signal we still have to solve a Linear Programming problem in R.

International audience; ABSTRACT XPC is responsible for DNA damage sensing in nucleotide excision repair (NER). Mutations in XPC lead to a defect in NER and to xeroderma pigmentosum (XP-C). Here, we analyzed the biochemical properties behind mutations found within three patients: one amino acid substitution (P334H, XP1MI, and GM02096), one amino acid incorporation in a conserved domain (697insVal, XP8BE, and GM02249), and a stop mutation (R579St, XP67TMA, and GM14867). Using these mutants, we demonstrated that HR23B stabilizes XPC on DNA and protects it from degradation. XPC recruits the transcription/repair factor TFIIH and stimulates its XPB ATPase activity to initiate damaged DNA opening. In an effort to understand the severity of XP-C phenotypes, we also demonstrated that single mutations in XPC perturb other repair processes, such as base excision repair (e.g., the P334H mutation prevents the stimulation of Ogg1 glycosylase because it thwarts the interaction between XPC and Ogg1), thereby leading to a deeper understanding of the molecular repair defect of the XP-C patients.

International audience; Xeroderma pigmentosum (XP) C is involved in the recognition of a variety of bulky DNA-distorting lesions in nucleotide excision repair. Here, we show that XPC plays an unexpected and multifaceted role in cell protection from oxidative DNA damage. XP-C primary keratinocytes and fibroblasts are hypersensitive to the killing effects of DNA-oxidizing agents and this effect is reverted by expression of wild-type XPC. Upon oxidant exposure, XP-C primary keratinocytes and fibroblasts accumulate 8,5'-cyclopurine 2'-deoxynucleosides in their DNA, indicating that XPC is involved in their removal. In the absence of XPC, a decrease in the repair rate of 8-hydroxyguanine (8-OH-Gua) is also observed. We demonstrate that XPC-HR23B complex acts as cofactor in base excision repair of 8-OH-Gua, by stimulating the activity of its specific DNA glycosylase OGG1. In vitro experiments suggest that the mechanism involved is a combination of increased loading and turnover of OGG1 by XPC-HR23B complex. The accumulation of endogenous oxidative DNA damage might contribute to increased skin cancer risk and account for internal cancers reported for XP-C patients.

Recently in Nature, Jaskelioff et al. (2010) demonstrated that multiple aging phenotypes in a mouse model of accelerated telomere loss can be reversed within 4 weeks of reactivating telomerase. This raises the major question of whether physiological aging, likely caused by a combination of molecular defects, may also be reversible.