KSHV MicroRNAs Mediate Cellular Transformation and Tumorigenesis by Redundantly Targeting Cell Growth and Survival Pathways

Kaposi''s sarcoma-associated herpesvirus (KSHV) is causally linked to several human cancers, including Kaposi''s sarcoma, primary effusion lymphoma and multicentric Castleman''s disease, malignancies commonly found in HIV-infected patients. While KSHV encodes diverse functional products, its mechanism of oncogenesis remains unknown. In this study, we determined the roles KSHV microRNAs (miRs) in cellular transformation and tumorigenesis using a recently developed KSHV-induced cellular transformation system of primary rat mesenchymal precursor cells. A mutant with a cluster of 10 precursor miRs (pre-miRs) deleted failed to transform primary cells, and instead, caused cell cycle arrest and apoptosis. Remarkably, the oncogenicity of the mutant virus was fully restored by genetic complementation with the miR cluster or several individual pre-miRs, which rescued cell cycle progression and inhibited apoptosis in part by redundantly targeting IκBα and the NF-κB pathway. Genomic analysis identified common targets of KSHV miRs in diverse pathways with several cancer-related pathways preferentially targeted. These works define for the first time an essential viral determinant for KSHV-induced oncogenesis and identify NF-κB as a critical pathway targeted by the viral miRs. Our results illustrate a common theme of shared functions with hierarchical order among the KSHV miRs.     

Decline of neural tube defects cases after a folic acid campaign in Nuevo León,México

BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis.     

L-Lactic acid production from raw cassava starch in a circulating loop bioreactor with cells immobilized in loofa (Luffa cylindrica)

l-Lactic acid was produced from raw cassava starch, by simultaneous enzyme production, starch saccharification and fermentation in a circulating loop bioreactor with Aspergillus awamori and Lactococcus lactis spp. lactis immobilized in loofa sponge. A. awamori was immobilized directly in cylindrical loofa sponge while the L. lactis was immobilized in a loofa sponge alginate gel cube. In the loofa sponge alginate gel cube, the sponge serves as skeletal support for the gel with the cells. The alginate gel formed a hard outer layer covering the soft porous gel inside. By controlling the rate and frequency of broth circulation between the riser and downcomer columns, the riser could be maintained under aerobic condition while the downcomer was under anaerobic condition. Repeated fed-batch l-lactic acid production was performed for more than 400 h and the average lactic acid yield and productivity from raw cassava starch were 0.76 g lactic acid g^–1 starch and 1.6 g lactic acid l^–1 h^–1, respectively.     

Fallow management for steppe bird conservation: the impact of cultural practices on vegetation structure and food resources

The potential of fallow lands to favor farmland bird conservation is widely recognized. Since fallows provide key resources for birds within the agricultural matrix, such as nesting sites, shelter and forage, complete understanding of the effect of field-management strategies on vegetation structure and food is essential to fulfill bird requirements and improve habitat management. In this study we experimentally compare the most common field practices (ploughing, shredding, herbicide application and cover cropping) on fallow lands by assessing the resources they provide for birds in terms of vegetation structure and food resources (leaf and seed availability), as well as the economic costs of their implementation. Fallow management treatments are ranked for six target species in a lowland area of the north-eastern Iberian Peninsula, according to the available information on their requirements. The different agronomic practices offer various quantities and types of resources, highlighting the importance of fallow management in bird conservation. Shredding and early herbicide application (February) are estimated to be good practices for Little Bustard (Tetrax tetrax) and Calandra Lark (Melanocorypha calandra), providing both favorable habitat and foraging conditions, while being economical. Meanwhile, superficial tillage in spring is found to be optimum for the rest of the species tested, despite being among the poorest food providers. Alternating patches of the best treatments would improve the effectiveness of agri-environmental schemes by maximizing the harboring habitat for the endangered species.     

Viral Cyclin promotes KSHV-induced cellular transformation and tumorigenesis by overriding contact inhibition

Kaposi sarcoma-associated herpesvirus (KSHV) is a tumor virus encoding several proto-oncogenes. However, the roles of these viral genes in KSHV-induced tumorigenesis have not been defined. In this study, we used a recently developed model of KSHV-induced cellular transformation and tumorigenesis combining with a reverse genetic system to examine the role of a KSHV latent gene vCyclin (ORF72), a cellular Cyclin D2 homolog, in KSHV-induced oncogenesis. Deletion of vCyclin did not affect cell proliferation and cell cycle progression at a low-density condition, when cells were at an active proliferation state. However, vCyclin mutant cells were contact-inhibited and arrested at G₁ phase at a high-density condition. As a result, vCyclin mutant cells formed less and smaller colonies in soft agar assay. Nude mice inoculated with vCyclin mutant cells had reduced tumor incidence and extended tumor latency and survival compared with mice inoculated with wild-type (WT) virus-infected cells. WT but not mutant virus effectively induced Cyclin-dependent kinase inhibitor p27/Kip1 Ser10 phosphorylation and cytoplasmic relocalization. shRNA knockdown of p27 released the blockage of the mutant cells from cell cycle arrest at G₁ phase at a high-density condition. Together, these results indicate that vCyclin primarily functions to enhance cellular transformation and tumorigenesis by promoting cell cycle progression and cell proliferation at a contact-inhibited condition.     

Medicinal plants used by latino healers for women’s health conditions in New York City

This paper examines the use of medicinal plants by Latino healers in New York City to treat various women’s illnesses. Eight Latino healers collaborated on the study through consultations with female patients who had one of the following conditions as diagnosed by biomedically trained physicians: uterine fibroids, hot flashes, menorrhagia, or endometriosis. The study identified a total of 67 plant species prescribed by the healers in the form of mixtures or as individual plants. Voucher specimens were collected from local botánicas and identified by specialists at The New York Botanical Garden. Studies of immigrant traditional healers and the plants they use in an urban setting can provide interesting ethnobotanical data and information to assist in diagnosing conditions and contributing to treatment of patients from Latino as well as non-Latino communities.