Modulation of Telomeres in Alternative Lengthening of Telomeres Type I Like Human Cells by the Expression of Werner Protein and Telomerase

The alternative lengthening of telomeres (ALT) is a recombination-based mechanism of telomere maintenance activated in 5–20% of human cancers. In Saccharomyces cerevisiae, survivors that arise after inactivation of telomerase can be classified as type I or type II ALT. In type I, telomeres have a tandem array structure, with each subunit consisting of a subtelomeric Y′ element and short telomere sequence. Telomeres in type II have only long telomere repeats and require Sgs1, the S. cerevisiae RecQ family helicase. We previously described the first human ALT cell line, AG11395, that has a telomere structure similar to type I ALT yeast cells. This cell line lacks the activity of the Werner syndrome protein, a human RecQ helicase. The telomeres in this cell line consist of tandem repeats containing SV40 DNA, including the origin of replication, and telomere sequence. We investigated the role of the SV40 origin of replication and the effects of Werner protein and telomerase on telomere structure and maintenance in AG11395 cells. We report that the expression of Werner protein facilitates the transition in human cells of ALT type I like telomeres to type II like telomeres in some aspects. These findings have implications for the diagnosis and treatment of cancer

Vegetative Change on South Padre Island, Texas, over Twenty Years and Evaluation of Multispectral Videography in Determining Vegetative Cover and Species Identity

A comparative vegetation analysis of an island-wide transect of South Padre Island, Texas, was conducted in 1997 using aerial multispectral digital videography and line intercept ground truth techniques to assess the usefulness of videography in estimating vegetative cover and species identifications. Ground truth data were used to assess vegetative change occurring in the 20 years since the report of Judd et al. (1977) on the vegetation of South Padre Island. Estimates of total cover by ground truth and remote sensing techniques were similar (2.45% difference) on South Padre Island. Thus, airborne multispectral digital videography is an effective technique for assessing changes in total vegetative cover of Texas barrier islands. This technique will be an effective tool for documenting changes in total cover on barrier islands due to natural perturbations such as hurricanes and human disturbances including vehicular traffic. Imagery obtained at altitudes of 200 m or greater did not permit discrimination of dominant species in each of an island\u27s topographic zones. However, acquisition of imagery at a time of the year when dominant species are in specific phenological stages, such as flowering, and at a lower altitude may facilitate their recognition. Comparison of data from a single trans-island transect in 1997 with data from three trans-island transects and 18 transects across the foreshore, backshore, and primary dunes in 1977 suggests that there has been a marked decrease in species richness of the backshore and primary dune zones of South Padre Island. There also was a change in dominant species in the backshore zone. These changes in species richness and dominance may be largely attributable to vehicular traffic in these zones. - Un análisis comparativo de la vegetación de un transecto transinsular de la isla South Padre en el estado de Texas fue realizado en 1997 usando videografía aérea multiesprectral digital y técnicas de validación de intercepción linear terrestre para evaluar la utilidad de la videografía en la estimación de la cobertura vegetal e identificación de especies. Los datos de estudios de validación terrestre fueron utilizados para evaluar el cambio vegetativo que ocurrió durante 20 años después del informe de Judd et al (1977) sobre la vegetación de la isla South Padre. Las estimaciones de la cobertura total mediante técnicas de validación terrestres y de medición remota fueron similares (2.45% de diferencia) en la isla South Padre. Por lo tanto, la videografía multiesprectral digital aérea se considera una técnica eficaz para evaluar cambios en la cobertura vegetal de las islas barrera de Texas. Esta técnica será una herramienta efectiva para documentar los cambios de cobertura total en las islas barrera debido a las perturbaciones naturales tales como huracanes y disturbios humanos como tráfico vehicular. Las imágenes obtenidas en altitudes de 200 metros o mayores no permitieron la discriminación de las especies dominantes de las varias zonas topográficas de una isla. Sin embargo, la adquisición de imágenes de una época del año en que las especies dominantes están en etapas fenológicas específicas, tales como la floración, y desde una altitud menor, puede facilitar su reconocimiento. Al comparar datos de un transecto transinsular de 1977 con los de tres transectos transinsulares y de 18 transectos correspondientes a la parte frontal, trasera, y de las dunas primarias de la isla en 1977, se sugiere que ha habido una marcada disminución en la riqueza de especies en la parte trasera y en la zona de dunas primarias de la isla South Padre. También hubo un cambio de especies dominantes en la zona trasera. Estos cambios en la riqueza y dominancia de especies pueden ser atribuidos en gran parte al tráfico vehicular en estas zonas

Activity of 2-Aryl-2-(3-indolyl)acetohydroxamates Against Drug-Resistant Cancer Cells

Many types of tumor, including glioma, melanoma, non-small cell lung, esophageal, head and neck cancer, among others, are intrinsically resistant to apoptosis induction and poorly responsive to current therapies with proapoptotic agents. In addition, tumors often develop multi-drug resistance based on the cellular efflux of chemotherapeutic agents. Thus, novel anticancer agents capable of overcoming these intrinsic or developed tumor resistance mechanisms are urgently needed. We describe a series of 2-aryl-2-(3-indolyl)acetohydroxamic acids, which are active against apoptosis- and multidrug-resistant cancer cells as well as glioblastoma neurosphere stem-like cell cultures derived from patients. Thus, the described compounds serve as a novel chemical scaffold for the development of potentially highly effective clinical cancer drugs

Evaluating the efficacy of commercially available aflatoxin binders for decreasing the effects of aflatoxicosis on Pacific white shrimp Litopenaeus vannamei

Feeding aflatoxin-contaminated diets to shrimp juveniles reduces feed intake and growth rate, suppresses the immune system, causes hepatic lesions, and, in some cases, decreases survival rates. There is scarce information on the effectiveness of commercially available aflatoxin binders to reduce aflatoxicosis in shrimp. Goals. We investigated the effect of corn that was naturally contaminated with aflatoxins on the growth performance and nitrogen retention efficiency of white shrimp juveniles L. vannamei and the potential of three commercially available anti-aflatoxin additives. Methods. 20 tanks (60L) were stocked with 10 shrimp weighing 210±4mg. Tanks were divided into five treatments with four replicates each. Shrimp were fed twice daily with either the contaminated diet (75 ?g kg1 total aflatoxins), the contaminated diet supplemented with 2 g kg-1 Aflabalan®, 2 g kg-1 Mycosorb®, and 2.5 g kg-1 Mycoflix plus®, or the uncontaminated diet to the control group for 42 days. Results. In terms of the diet containing aflatoxin without binding agents, the consumption, growth rate, and nitrogen-retention efficiency were significantly lower than the control treatment. The experimental diets did not affect the feed conversion ratio or survival rates in any treatment. The inclusion of any of the aflatoxin binders evaluated in the present study did not produce growth rates comparable to those of shrimp fed the uncontaminated diet. Conclusions. Aflatoxins decreased growth performance in a population of white shrimp juveniles L. vannamei. Although all the aflatoxin binders evaluated in this study caused an improvement, they were not effective in reversing all the negative effects caused by feeding aflatoxin-contaminated diets to white shrimp juveniles L. vannamei

Silencing microRNA-134 produces neuroprotective and prolonged seizure-suppressive effects

Temporal lobe epilepsy is a common, chronic neurological disorder characterized by recurrent spontaneous seizures. MicroRNAs (miRNAs) are small, noncoding RNAs that regulate post-transcriptional expression of protein-coding mRNAs, which may have key roles in the pathogenesis of neurological disorders. In experimental models of prolonged, injurious seizures (status epilepticus) and in human epilepsy, we found upregulation of miR-134, a brain-specific, activity-regulated miRNA that has been implicated in the control of dendritic spine morphology. Silencing of miR-134 expression in vivo using antagomirs reduced hippocampal CA3 pyramidal neuron dendrite spine density by 21% and rendered mice refractory to seizures and hippocampal injury caused by status epilepticus. Depletion of miR-134 after status epilepticus in mice reduced the later occurrence of spontaneous seizures by over 90% and mitigated the attendant pathological features of temporal lobe epilepsy. Thus, silencing miR-134 exerts prolonged seizure-suppressant and neuroprotective actions; determining whether these are anticonvulsant effects or are truly antiepileptogenic effects requires additional experimentation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Can Blood Flow Restricted Exercise Improve Ham:Quad Ratios Better Than Traditional Training?

International Journal of Exercise Science 12(4): 1080-1093, 2019. Muscular deficiencies between the quadriceps and hamstrings are prevalent among women and often lead to knee injury and ACL tears. The purpose of this study was to examine whether short term resistance training with or without blood flow restriction (BFR) could improve hamstring:quadricep ratios (H:Q) and reduce the chance for injury. Women (n = 14; 18-25 yrs) were randomly assigned to either a traditional resistance training (RT: n = 8) or BFR resistance training in combination with traditional RT (RT+BFR: n = 6) group. Subjects trained 3 days/week for 6 weeks. The RT group completed 3 sets of 10 reps at 70% of their one-repetition maximum (1RM) with 1-minute rest between sets. The RT+BFR group completed the first 5 exercises similar to the RT group but performed the two-leg hamstring curl under blood flow restriction at 50% of occlusive pressure and 30% 1RM, completing 4 sets (30, 15, 15, 15) with 30 seconds rest between sets. Training effects were assessed using a two-way repeated measures ANOVA. Statistical significance was set at p≤0.05. There were significant (p \u3c 0.05) main effects for time, with all muscle groups increasing strength but no significant main effects or interaction for the H:Q ratios at four testing speeds (60°/s, 180°/s, 240°/s, and 300º/s). This study found that hamstring strength with low load (30% 1RM) BFR training was improved to a similar extent as the hamstrings trained with the traditional high load (75% 1RM) program even though less external weight was used during training. H:Q ratios showed small non-significant increases post-training for both groups

Obesity Enhances Nongenomic Estrogen Receptor Crosstalk with the PI3K/Akt and MAPK Pathways to Promote in Vitro Measures of Breast Cancer Progression

Epidemiological and clinical studies indicate that obesity is associated with a worse postmenopausal breast cancer prognosis and an increased risk of endocrine therapy resistance. However, the mechanisms mediating these effects remain poorly understood. Here we investigate the molecular pathways by which obesity-associated circulating factors in the blood enhance estrogen receptor alpha (ER alpha) positive breast cancer cell viability and growth. Methods: Blood serum was collected from postmenopausal breast cancer patients and pooled by body mass index (BMI) category (Control: 18.5 to 24.9 kg/m(2); Obese: >= 30.0 kg/m(2)). The effects of patient sera on MCF-7 and T47D breast cancer cell viability and growth were examined by MTT and colony formation assays, respectively. Insulin-like growth factor receptor 1(IGF-1R), Akt, and ERK1/2 activation and genomic ER alpha activity were assessed to determine their possible contribution to obese patient sera-induced cell viability and growth. To further define the relative contribution of these signaling pathways, cells grown in patient sera were treated with various combinations of ER alpha, PI3K/Akt and MAPK targeted therapies. Comparisons between cells exposed to different experimental conditions were made using one-way analysis of variance (ANOVA) and Student's t test. Results: Cells grown in media supplemented with obese patient sera displayed greater cell viability and growth as well as IGF-1R, Akt and ERK1/2 activation relative to control sera. Despite the lack of a significant difference in genomic ER alpha activity following growth in obese versus control patient sera, we observed a dramatic reduction in cell viability and growth after concurrent inhibition of the ER alpha and PI3K/Akt signaling pathways. Further, we demonstrated that ER alpha inhibition was sufficient to attenuate obese serum-induced Akt and ERK1/2 activation. Together, these data suggest that obesity promotes greater ER alpha positive breast cancer cell viability and growth through enhanced crosstalk between nongenomic ER alpha signaling and the PI3K/Akt and MAPK pathways. Conclusions: Circulating factors in the serum of obese postmenopausal women stimulate ER alpha positive breast cancer cell viability and growth by facilitating non-genomic ER alpha crosstalk with the PI3K/Akt and MAPK signaling pathways. These findings provide valuable insight into one mechanism by which obesity may promote ER alpha positive postmenopausal breast cancer progression and endocrine therapy resistance.US Department of Defense, Breast Cancer Research Program (BCRP) of the Congressionally Directed Medical Research Programs (CDMRP) W81XWH-11-1-0132Nutritional Science