Mariner: explore the Hi-Cs.

MOTIVATION: 3D chromatin structure plays an important role in regulating gene expression and alterations to this structure can result in developmental abnormalities and disease. While genomic approaches like Hi-C and Micro-C can provide valuable insights in 3D chromatin architecture, the resulting datasets are extremely large and difficult to manipulate. RESULTS: Here, we present mariner, a rapid and memory efficient tool to extract, aggregate, and plot data from Hi-C matrices within the R/Bioconductor environment. Mariner simplifies the process of querying and extracting contacts from multiple Hi-C files using a parallel and block-processing approach. Modular functions allow complete workflow customization for advanced users, yet all-in-one functions are available for running the most common types of analyses. Finally, tight integration with existing Bioconductor infrastructure enables complete analysis and visualization of Hi-C data in R. AVAILABILITY AND IMPLEMENTATION: Available on GitHub at https://github.com/EricSDavis/mariner and on Bioconductor at https://www.bioconductor.org/packages/release/bioc/html/mariner.html.

Involvement of the E2A basic helix-loop-helix protein in immunoglobulin heavy chain class switching.

The basic helix-loop-helix (bHLH) transcriptional factor E2A has previously been shown to play a critical role in early B cell development, with E2A knockout mice and Id1 transgenic mice showing an arrest at the pro-B cell stage of development. More recent data suggest that E2A, through an interaction with the immunoglobulin heavy chain 3' enhancer, might also regulate later events in B cell development such as heavy chain class switching. The patterns of E2A protein expression in secondary lymphoid tissues support a role in later stages of B cell maturation. In particular, immunostaining reveals upregulation of E2A protein in cells of the dark zone of the germinal center, the site of immunoglobulin heavy chain class switching. To examine the role of E2A in class switching, the inhibitory HLH protein Id1 was expressed in B cell lines which normally undergo spontaneous and inducible switching from IgM to IgA. The forced expression of Id1 in these cell lines effectively blocked class switching. This Id1 blockade of class switching did not occur via downregulation of immunoglobulin heavy chain germline transcription or through inhibition of cell cycling. Furthermore, Id1 inhibited spontaneous and, to a lesser degree, cytokine inducible class switching. From these data, we conclude that E2A plays an important role in the class switching process.

Elevated interleukin-6 levels in the ovarian hyperstimulation syndrome: ovarian immunohistochemical localization of interleukin-6 signal.

OBJECTIVE: To examine the production and immunolocalization of interleukin-6 (IL-6) in patients with the ovarian hyperstimulation syndrome. METHODS: The study group consisted of patients with ovarian hyperstimulation syndrome (n = 9) from whom serum and ascites samples were obtained. The control samples used were serum (n = 10) and peritoneal (n = 16) and follicular fluids (n = 8) from healthy individuals. Follicular fluid (n = 40) and serial serum samples were also obtained from patients undergoing menotropin stimulation for in vitro fertilization (IVF) before (n = 10) and after ovulation (n = 34). Interleukin-6 measurements were performed with a sensitive immunoassay and confirmed with a bioassay. Immunohistochemical localization of IL-6 was performed with a mouse monoclonal antibody in normal premenopausal (n = 5) and postmenopausal ovaries (n = 5), as well as with cells from stimulated follicular fluid aspirates (n = 3). RESULTS: We found significantly higher serum and ascites IL-6 levels in ovarian hyperstimulation syndrome (mean 18.8 +/- 1.1 and 810.8 +/- 60.7 pg/mL, respectively) compared with postovulatory serum and peritoneal fluid from normal controls (mean 4.4 +/- .69 and 44.7 +/- 7.5 pg/mL, respectively) (P < .001) or serum after menotropin stimulation (13.1 +/- 1.1 pg/mL) (P < .001). At the time of ovulation, follicular fluid IL-6 levels (normal controls, mean 9 +/- 2.1 pg/mL; menotropin stimulation, mean 10.1 +/- 4 pg/mL) were higher than in preovulatory serum (normal controls, mean 4.5 +/- .8 pg/mL; menotropin stimulation, mean 6.3 +/- 1.4 pg/mL) (P < .001). Immunohistochemical localization of IL-6 revealed intense staining in corpora lutea and theca cells from large antral follicles and luteinized granulosa cells in follicular aspirates after menotropin stimulation. CONCLUSION: Interleukin-6 levels are markedly elevated in the ovarian hyperstimulation syndrome when compared with controls. The higher follicular fluid IL-6 levels seen suggest local secretion of this cytokine. Immunohistochemical correlation demonstrated IL-6 within ovarian theca cells. These findings suggest a local role for IL-6 both in normal and stimulated ovarian function. Whether IL-6 is directly responsible for the clinical manifestations of this syndrome is unclear. However, when produced in massive amounts, the pro-inflammatory effects of IL-6 may contribute to its pathogenesis and perhaps serve as a marker for the disease.

Core needle biopsy and fine-needle aspiration in the diagnosis of bone and soft-tissue lesions.

Although core needle biopsy (CNB) and fine needle aspiration (FNA) procedures are widely used for the diagnosis of epithelial neoplasms, these procedures have not gained popularity on patients suspected of having bone or soft-tissue neoplasms. This article describes the University of Texas, M.D. Anderson Cancer Center experience with CNB and FNA procedures in bone and soft tissue performed in over 800 patients.

The Barangay service point officers: their performance and potentials.

PIP: The Strengthening BSPO (barangay service point officer) Operations project aims to strengthen the outreach structure at the BSPO level by hastening its attainment of self-sufficiency and making it more responsive to community needs and demands. It has 2 specific objectives: to provide policymakers and managers of the outreach project with a research-based assessment of current organizational procedures, practices, and factors taht hindet the effectiveness od organizations and operations at the BSPO level; and to provide Popcom's decision makers with alternative means for evolving regional and national action plans to improve BSPO operations. This discussion presents the highlights of a 3rd major project report on the "Qualitative Survey Research on BSPOs and BSPO Operations." The report covers the outcome of focus group discussions (FGDs) conducted in 3 selected regions, with resondents consisting of BSPOs, fulltime outreach workers (FTOWs), married couples of reproductive age (MCRA), and barangay captains. 6 priority issues were taken up in the FGDs conducted: selection and recruitment of BSPOs; taining; incentives and awards; perception of roles and functions; functional relationships of BSPOs and other workers; and BSPO associations. The FTOWs considered the following qualities when choosing BSPOs: influence in the community; accessibility to neighbors; approachability and friendliness; respectability in the community; belief in family planning; satisfaction with family planning use; and ability to motivate people. Before starting volunteer work, BSPOs are trained formally for 3 days. While BSPOs recognize the importance of their role in community development, they are hesitant to accept too many tasks. They perceive the replenishment of contraceptive supply to be their primary function. Record keeping, home visits, information dissemination, and motivation are considered secondary. Popcom regional offices have incentive programs meant to cover all BSPOs. There also are incentives for outstanding BSPO performances. The available incentives are not always enough. Some BSPOs experience strained working relationshiops with workers of other agencies. Coordination among the various groups is limited. Experience has shown that the performance of BSPOs in general has not come up to the program's expectations because of improper recruitment practices, inaccurate communication of roles and functions, poor trining, inadequate incentives, and lack of coordination.^ieng