Telomerase
Telomere
RNA
Telomere Homeostasis
DNA-Binding Proteins
Telomere-Binding Proteins
Dyskeratosis Congenita
Cell Aging
Euplotes
Telomere Shortening
Holoenzymes
Telomeric Repeat Binding Protein 1
RNA, Protozoan
DNA Nucleotidylexotransferase
Coiled Bodies
Catalytic Domain
Gene Expression Regulation, Enzymologic
Base Sequence
Tumor Cells, Cultured
Mutation
Cell Division
Nucleic Acid Conformation
Cell Line, Transformed
Molecular Sequence Data
G-Quadruplexes
RNA, Messenger
DNA Primers
Reverse Transcriptase Polymerase Chain Reaction
Repetitive Sequences, Nucleic Acid
Telomeric Repeat Binding Protein 2
Cell Transformation, Neoplastic
Templates, Genetic
RNA, Long Noncoding
Proto-Oncogene Proteins c-myc
Kluyveromyces
Tankyrases
Microscopy, Electron
Knowledge Bases
Education, Graduate
Telomerase reverse transcriptase gene is a direct target of c-Myc but is not functionally equivalent in cellular transformation. (1/3684)
The telomerase reverse transcriptase component (TERT) is not expressed in most primary somatic human cells and tissues, but is upregulated in the majority of immortalized cell lines and tumors. Here, we identify the c-Myc transcription factor as a direct mediator of telomerase activation in primary human fibroblasts through its ability to specifically induce TERT gene expression. Through the use of a hormone inducible form of c-Myc (c-Myc-ER), we demonstrate that Myc-induced activation of the hTERT promoter requires an evolutionarily conserved E-box and that c-Myc-ER-induced accumulation of hTERT mRNA takes place in the absence of de novo protein synthesis. These findings demonstrate that the TERT gene is a direct transcriptional target of c-Myc. Since telomerase activation frequently correlates with immortalization and telomerase functions to stabilize telomers in cycling cells, we tested whether Myc-induced activation of TERT gene expression represents an important mechanism through which c-Myc acts to immortalize cells. Employing the rat embryo fibroblast cooperation assay, we show that TERT is unable to substitute for c-Myc in the transformation of primary rodent fibroblasts, suggesting that the transforming activities of Myc extend beyond its ability to activate TERT gene expression and hence telomerase activity. (+info)Activation of telomerase and its association with G1-phase of the cell cycle during UVB-induced skin tumorigenesis in SKH-1 hairless mouse. (2/3684)
Telomerase is a ribonucleoprotein enzyme that adds hexanucleotide repeats TTAGGG to the ends of chromosomes. Telomerase activation is known to play a crucial role in cell-immortalization and carcinogenesis. Telomerase is shown to have a correlation with cell cycle progression, which is controlled by the regulation of cyclins, cyclin dependent kinases (cdks) and cyclin dependent kinase inhibitors (cdkis). Abnormal expression of these regulatory molecules may cause alterations in cell cycle with uncontrolled cell growth, a universal feature of neoplasia. Skin cancer is the most prevalent form of cancer in humans and the solar UV radiation is its major cause. Here, we investigated modulation in telomerase activity and protein expression of cell cycle regulatory molecules during the development of UVB-induced tumors in SKH-1 hairless mice. The mice were exposed to 180 mjoules/cm2 UVB radiation, thrice weekly for 24 weeks. The animals were sacrificed at 4 week intervals and the studies were performed in epidermis. Telomerase activity was barely detectable in the epidermis of non-irradiated mouse. UVB exposure resulted in a progressive increase in telomerase activity starting from the 4th week of exposure. The increased telomerase activity either persisted or further increased with the increased exposure. In papillomas and carcinomas the enzyme activity was comparable and was 45-fold higher than in the epidermis of control mice. Western blot analysis showed an upregulation in the protein expression of cyclin D1 and cyclin E and their regulatory subunits cdk4 and cdk2 during the course of UVB exposure and in papillomas and carcinomas. The protein expression of cdk6 and ckis viz. p16/Ink4A, p21/Waf1 and p27/Kip1 did not show any significant change in UVB exposed skin, but significant upregulation was observed both in papillomas and carcinomas. The results suggest that telomerase activation may be involved in UVB-induced tumorigenesis in mouse skin and that increased telomerase activity may be associated with G1 phase of the cell cycle. (+info)Telomerase activity is sufficient to allow transformed cells to escape from crisis. (3/3684)
The introduction of simian virus 40 large T antigen (SVLT) into human primary cells enables them to proliferate beyond their normal replicative life span. In most cases, this temporary escape from senescence eventually ends in a second proliferative block known as "crisis," during which the cells cease growing or die. Rare immortalization events in which cells escape crisis are frequently correlated with the presence of telomerase activity. We tested the hypothesis that telomerase activation is the critical step in the immortalization process by studying the effects of telomerase activity in two mortal SVLT-Rasval12-transformed human pancreatic cell lines, TRM-6 and betalox5. The telomerase catalytic subunit, hTRT, was introduced into late-passage cells via retroviral gene transfer. Telomerase activity was successfully induced in infected cells, as demonstrated by a telomerase repeat amplification protocol assay. In each of nine independent infections, telomerase-positive cells formed rapidly dividing cell lines while control cells entered crisis. Telomere lengths initially increased, but telomeres were then maintained at their new lengths for at least 20 population doublings. These results demonstrate that telomerase activity is sufficient to enable transformed cells to escape crisis and that telomere elongation in these cells occurs in a tightly regulated manner. (+info)Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (4/3684)
Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation. (+info)Cloning and characterization of the promoter region of human telomerase reverse transcriptase gene. (5/3684)
Activation of telomerase is one of the rate-limiting steps in human cell immortalization and carcinogenesis Human telomerase is composed of at least two protein subunits and an RNA component. Regulation of expression of the catalytic subunit, human telomerase reverse transcriptase (hTERT), is suggested as the major determinant of the enzymatic activity. We report here the cloning and characterization of the 5'-regulatory region of the hTERT gene. The highly GC-rich content of the 5' end of the hTERT cDNA spans to the 5'-flanking region and intron 1, making a CpG island. A 1.7-kb DNA fragment encompassing the hTERT gene promoter was placed upstream of the luciferase reporter gene and transiently transfected into human cell lines of fibroblastic and epithelial origins that differed in their expression of the endogenous hTERT gene. Endogenous hTERT-expressing cells, but not nonexpressing cells, showed high levels of luciferase activity, suggesting that the regulation of hTERT gene expression occurs mainly at the transcriptional level. Additional luciferase assays using a series of constructs containing unidirectionally deleted fragments revealed that a 59-bp region (-208 to -150) is required for the maximal promoter activity. The region contains a potential Myc oncoprotein binding site (E-box), and cotransfection of a c-myc expression plasmid markedly enhanced the promoter activity, suggesting a role of the Myc protein in telomerase activation. Identification of the regulatory regions of the hTERT promoter sequence will be essential in understanding the molecular mechanisms of positive and negative regulation of telomerase. (+info)A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. (6/3684)
Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor-sensitive, mammalian senescence mechanism unrelated to telomere maintenance. (+info)Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. (7/3684)
To study the effect of continued telomere shortening on chromosome stability, we have analyzed the telomere length of two individual chromosomes (chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both chromosomes decreased with increasing generations of mTER-/- mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length of all chromosomes. Interestingly, the most frequent fusions found in mTER-/- cells were homologous fusions involving chromosome 2. Immortal cultures derived from the primary mTER-/- cells showed a dramatic accumulation of fusions and translocations, revealing that continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes 2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during the growth of the immortal mTER-/- cells, telomere length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER-/- cells to grow indefinitely and form tumors. (+info)Induction of telomerase activity in v-myc-transformed avian cells. (8/3684)
Telomerase activity is detectable in the majority of tumors or immortalized cell lines, but is repressed in most normal human somatic cells. It is generally assumed that reactivation of telomerase prevents the erosion of chromosome ends which occurs in cycling cells and, hence, hinders cellular replicative senescence. Here, we show that the expression of v-Myc oncoprotein by retroviral infection of telomerase-negative embryonal quail myoblasts and chicken neuroretina cells is sufficient for reactivating telomerase activity, earlier than telomere shortening could occur. Furthermore, the use of a conditional v-Myc-estrogen receptor protein (v-MycER) causes estrogen-dependent expression of detectable levels of telomerase activity in recently infected chick embryo fibroblasts and neuroretina cells. We conclude that the high levels of telomerase activity in v-Myc-expressing avian cells are not the mere consequence of transformation or of a differentiative block, since v-Src tyrosine kinase, which prevents terminal differentiation and promotes cell transformation, fails to induce telomerase activity. (+info)Dyskeratosis congenita is a rare genetic disorder that affects the bone marrow, skin, and other organs. It is characterized by a defect in the maturation of hematopoietic stem cells, leading to a triad of symptoms:
1. Poor immune function
2. Bone marrow failure
3. Skin changes (such as poikiloderma, telangiectasia, and pigmentary changes)
The disorder is caused by mutations in genes involved in hematopoiesis and DNA repair, leading to a decrease in the number of blood cells and an increased risk of infections, bleeding, and cancer. Treatment options for dyskeratosis congenita include bone marrow transplantation, immunosuppressive therapy, and supportive care to manage symptoms and prevent complications. The prognosis for the disorder is generally poor, with most patients dying in childhood or adolescence due to complications related to bone marrow failure and/or cancer.
Explanation: Neoplastic cell transformation is a complex process that involves multiple steps and can occur as a result of genetic mutations, environmental factors, or a combination of both. The process typically begins with a series of subtle changes in the DNA of individual cells, which can lead to the loss of normal cellular functions and the acquisition of abnormal growth and reproduction patterns.
Over time, these transformed cells can accumulate further mutations that allow them to survive and proliferate despite adverse conditions. As the transformed cells continue to divide and grow, they can eventually form a tumor, which is a mass of abnormal cells that can invade and damage surrounding tissues.
In some cases, cancer cells can also break away from the primary tumor and travel through the bloodstream or lymphatic system to other parts of the body, where they can establish new tumors. This process, known as metastasis, is a major cause of death in many types of cancer.
It's worth noting that not all transformed cells will become cancerous. Some forms of cellular transformation, such as those that occur during embryonic development or tissue regeneration, are normal and necessary for the proper functioning of the body. However, when these transformations occur in adult tissues, they can be a sign of cancer.
See also: Cancer, Tumor
Word count: 190
Telomerase
Telomerase RNA component
Telomerase reverse transcriptase
ACD (gene)
RNA
Werner syndrome
Tetrahymena thermophila
Muse cell
BioViva
Cell cycle withdrawal
Nucleolin
Ageing
Geron Corporation
Stem cell
Lobster
Eternal youth
Life Length
Juli Feigon
Mesothelioma
Biological immortality
Michael D. West
Telomeric repeat-containing RNA
Reptin
Telomeres in the cell cycle
List of RNAs
Immortality
Pediatric ependymoma
DNA
Disposable soma theory of aging
Bryant Villeponteau
Telomerase mutations in families with idiopathic pulmonary fibrosis
JCI -
Telomerase reverse transcriptase promotes cancer cell proliferation by augmenting tRNA expression
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Telomerase Reverse Transcriptase Market Size, Share, Trends and Forecast 2022-2030 - PR Bulletin
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Renovage induces heat shock proteins, not telomerase. This is not DNA repair. This is bogus. | BareFacedTruth.com
Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for...
The correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase...
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Chemists inhibit a critical gear of cell immortality
Telomere length5
- Well let's look at some of the experiments with telomerase activation to improve telomere length. (antiaging-systems.com)
- Cancer cells, on the other hand, hijack telomerase and re-express it to maintain telomere length, making them impervious to aging-related death. (newswise.com)
- TERC gene mutations lead to telomerase dysfunction, impaired maintenance of telomeres, and reduced telomere length. (medlineplus.gov)
- Results suggest that WF inhalation increased telomere length without affecting telomerase in whole brain. (cdc.gov)
- Germ cells (eggs and sperm) and stem cells contain an enzyme, telomerase, that restores telomere length. (cdc.gov)
TERT6
- Transcriptional reactivation of telomerase reverse transcriptase (TERT) reconstitutes telomerase activity in the majority of human cancers. (jci.org)
- Telomerase is a ribonucleoprotein composed of an internal telomerase RNA template (TERC) and the enzyme, telomerase reverse transcriptase (TERT). (tocris.com)
- BACKGROUND: Genome-wide association studies have implicated single nucleotide polymorphisms (SNPs) in 7 genes as glioma risk factors, including 2 (TERT, RTEL1) involved in telomerase structure/function. (duke.edu)
- 115 patients with mutations in telomerase reverse transcriptase ( TERT ) (n=75), telomerase RNA component ( TERC ) (n=7), regulator of telomere elongation helicase 1 ( RTEL1 ) (n=14) and poly(A)-specific ribonuclease ( PARN ) (n=19) were identified and clinical data were analysed. (ersjournals.com)
- Mutations in the protein component of telomerase ( TERT ) and the RNA component of the enzyme ( TERC ) lead to short telomere lengths and familial pulmonary fibrosis [ 6 , 7 ]. (ersjournals.com)
- The other major component of telomerase, which is produced from a gene called TERT , is known as hTERT. (medlineplus.gov)
Enzyme called telomerase2
- The TERC gene provides instructions for making one component of an enzyme called telomerase. (medlineplus.gov)
- Normally when telomeres wear down, an enzyme called telomerase rebuilds them. (psychologicalscience.org)
Mutations4
- Germ-line mutations in the genes hTERT and hTR, encoding telomerase reverse transcriptase and telomerase RNA, respectively, cause autosomal dominant dyskeratosis congenita, a rare hereditary disorder associated with premature death from aplastic anemia and pulmonary fibrosis. (nih.gov)
- Mutations in the genes encoding telomerase components can appear as familial idiopathic pulmonary fibrosis. (nih.gov)
- In this study, a novel, genetically engineered adenovirus was designed to lyse SFs that exhibit high telomerase activity and p53 mutations, and its effects as a novel therapeutic strategy were assessed in an experimental arthritis model. (ncku.edu.tw)
- Mutations in the TERC gene reduce or eliminate the function of telomerase, which allows telomeres to become abnormally short as cells divide. (medlineplus.gov)
HTERT1
- others change the way hTR interacts with hTERT or other components of the telomerase enzyme. (medlineplus.gov)
Chromosomes7
- Zappulla's research focuses on an enzyme found in cells, called telomerase, which lengthens repetitive bits of DNA at the end of chromosomes. (newswise.com)
- But to develop such drugs, scientists need a better understanding of how telomerase gets to and extends the chromosomes' ends. (newswise.com)
- He published research in 2015 showing how two proteins, Ku and Sir4, interact to lure telomerase near the tips of yeast chromosomes. (newswise.com)
- The crystal structures show how Ku binds to both the RNA in telomerase and the Sir4 protein on the chromosomes, as we had proposed in our 2015 study. (newswise.com)
- Telomerase maintains structures called telomeres, which are composed of repeated segments of DNA found at the ends of chromosomes. (medlineplus.gov)
- Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides. (medlineplus.gov)
- It provides a template for creating the repeated sequence of DNA that telomerase adds to the ends of chromosomes. (medlineplus.gov)
Overexpression2
- Overexpression of telomerase is key component of the transformation process in many malignant cancer cells. (tocris.com)
- The successful immortalization of neural progenitor cells via the overexpression of telomerase prompts several questions for those intending to develop somatic stem cell therapies for neurological disease. (nature.com)
Gene1
- Is telomerase gene therapy a gateway to the Zombie apolcalypse? (rechargebiomedical.com)
Chromosome3
- There appear to be multiple regulatory steps that precisely control telomerase and recruit it to the shortest chromosome ends where and when it's needed," says Zappulla, who has worked to reveal these processes. (newswise.com)
- He believes that Sir4 acts as a landing pad to attract telomerase preferentially to short chromosome tips that need an extension. (newswise.com)
- When Zappulla first saw the results, he says that they immediately answered one of his questions about how telomerase interacted with Ku and Sir4 to attach to the chromosome end. (newswise.com)
Fibroblasts1
- 10. Kamata N, Fujimoto R, Tomonari M, Taki M, Nagayama M, Yasumoto S. Immortalization of human dental papilla, dental pulp, periodontal ligament cells and gingival fibroblasts by telomerase reverse transcriptase. (bvsalud.org)
Metabolism1
- These discoveries suggest that alterations in immune responses, barrier function, metabolism and telomerase activity may be implicated in the genetic risks for fibrotic diseases. (frontiersin.org)
Genes2
Promoter1
- An E1B-55-kd-deleted adenovirus driven by the human telomerase reverse transcriptase promoter was constructed (designated Ad.GS1). (ncku.edu.tw)
Proteins3
- Renovage induces heat shock proteins, not telomerase. (barefacedtruth.com)
- For the current research, published Jan. 11 in Cell , Lei's team crystallized the baker's yeast versions of key telomerase-recruiting proteins, as well as a piece of the telomerase enzyme's RNA. (newswise.com)
- These experiments led to new insights into how telomerase-recruiting proteins work and interrelate in time and space. (newswise.com)
Genetics1
- Zappulla works in the department of molecular biology and genetics at Johns Hopkins, which is led by Carol Greider, Ph.D., who discovered telomerase in 1984 and shares the 2009 Nobel Prize for Physiology or Medicine with Elizabeth Blackburn and Jack W. Szostak for the finding. (newswise.com)
Dividing cells1
- Expression of telomerase is low in most normal cells although it is thought to be active in embryonic cells and some rapidly dividing cells of the immune system. (tocris.com)
TTAGGG1
- Telomerase is a reverse transcriptase enzyme that adds TTAGGG repeats to chromosomal ends during cell replication. (ersjournals.com)
Human2
- Human telomerase RNA expression and MIB-1 (Ki-67) proliferation index distinguish hemangioblastomas from metastatic renal cell carcinomas. (bvsalud.org)
- ATCC) were cultured as previously mentioned ( 4 ), as were THF cells (human telomerase life-extended cells) ( 5 ). (cdc.gov)
Reverse8
- QY Research Medical published a comprehensive research on Telomerase Reverse Transcriptase Market, which provides a business strategies, research & development activities, concise outline of the market valuation, valuable insights pertaining to market share, size, supply chain analysis, competitive landscape and regional proliferation of this industry. (prbulletin.com)
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- The report scope of Telomerase Reverse Transcriptase market covers the in-depth analysis, along with an overview of market dynamics such as driver, restraints that are expected to impact the market growth. (prbulletin.com)
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- All the major application areas for Telomerase Reverse Transcriptase are covered in this report and information is given on the important regions of the world where this market is likely to boom during the forecast period of 2021-2030 so that you can plan your strategies to enter this market accordingly. (prbulletin.com)
Mechanisms1
- This supports the hypothesis that telomerase-related mechanisms of telomere maintenance are more associated with gliomas that develop later in life than those utilizing telomerase-independent mechanisms (ie, alternative lengthening of telomeres). (duke.edu)
Proliferation1
- The present study analyzed the utility of proliferation potential in differentiating hemangioblastoma from RCC metastatic to the central nervous system using a MIB-1 (Ki-67) labeling index and assessment of expression of the RNA component of telomerase . (bvsalud.org)
Activity2
Experiments1
- In experiments looking at telomerase in baker's yeast, his lab showed that the Ku protein helps telomerase sense when a telomere is short. (newswise.com)
Rapidly2
- Telomerase is present in fetal cells to keep DNA from getting too clipped as cells multiply rapidly during early development, but then the enzyme is turned off, and telomeres erode over time, as part of the natural aging process of cells. (newswise.com)
- However, telomerase is highly active in cells that divide rapidly, such as cells that line the lungs and gastrointestinal tract, cells in bone marrow, and cells of the developing fetus. (medlineplus.gov)
Components1
- The telomerase enzyme consists of two major components that work together. (medlineplus.gov)
Short2
Cancer cells1
- Telomerase is also abnormally active in cancer cells, which grow and divide without control or order. (medlineplus.gov)
Normal cells1
- Although activating telomerase to immortalize normal cells is a theoretical possibility, its feasibility isn't known. (cdc.gov)
Body1
- Telomerase is the enzyme used within the body to help repair telomeres and when activated can help repair and lengthen them. (antiaging-systems.com)
Work1
- But Epel's work has shown time and again that early life stress - going as far back as the womb - disrupts the normal development of telomerase and leads to harmful cellular aging. (psychologicalscience.org)
Scientific3
- Tocris offers the following scientific literature for Telomerase to showcase our products. (tocris.com)
- In January 2011, the scientific journal- Nature - published the results with telomerase deficient mice. (antiaging-systems.com)
- Telomerase activators and nanovesicles are not FDA-approved to prevent or treat any disease and anecdotes are not scientific proof of efficacy. (rechargebiomedical.com)
Times2
- In recent times the discovery that the telomerase enzyme can lengthen telomeres has caused a great buzz in the antiaging and medical fraternity, they've caused both controversy and excitement, so what's it all about? (antiaging-systems.com)
- Telomerase allows these cells to divide many times without becoming damaged or undergoing apoptosis. (medlineplus.gov)