HABITAT USE BY GREATER SANDHILL CRANES IN WYOMING

Wyoming suppors approximately 20% of the Rocky Mountain population (RMP) of greater sandhill cranes (Grus canadensis tabida), as well as a number of whooping cranes (Grus americana) from the Grays Lake, Idaho flock. Cranes begin arriving on post-migration staging areas in Wyoming in mid-March and disperse to summer habitat in April or May, depending on snow cover. Fall pre-migration, staging peaks around mid-September; most cranes leave the state by 1 October. Wet meadows and gram fIelds were the major habitat types used by cranes in Wyoming 1985-1987. Use in these types ranged from 69- 100% of total observations in any given 2-week period. Important grains included barley, wheat and oats. Wet meadows were typically either seasonally flooded wetlands or flood-irrigated haylands. Alfalfa fields and cattailbulrush (Typha sp./Scirpus sp.) marshes were also important habitats for cranes

The Safe Zone--It\u27s not segregation

Let\u27s talk about the Safe Zone. Let\u27s talk about the creation of a ten room, single occupancy wing which is open to heterosexuals, allies, gays, lesbians, bisexual, transgendered, as well as thos who haven\u27t quite self-identified as… Let\u27s be realistic, the Safe Zone, as proposed, will not come close to housing every gay and lesbian on the University of Maine campus, nor is that its attempt

Identification of plant-derived alkaloids with therapeutic potential for myotonic dystrophy type I

Myotonic dystrophy type I (DM1) is a disabling neuromuscular disease with no causal treatment available. This disease is caused by expanded CTG trinucleotide repeats in the 3 UTR of the dystrophia myotonica protein kinase gene. On the RNA level, expanded (CUG)n repeats form hairpin structures that sequester splicing factors such as muscleblind-like 1 (MBNL1). Lack of availableMBNL1leads to misregulated alternative splicing of many target pre-mRNAs, leading to the multisystemic symptoms in DM1. Many studies aiming to identify small molecules that target the (CUG)n-MBNL1 complex focused on synthetic molecules. In an effort to identify new small molecules that liberate sequesteredMBNL1from (CUG)n RNA, we focused specifically on small molecules of natural origin. Natural products remain an important source for drugs and play a significant role in providing novel leads and pharmacophores for medicinal chemistry. In a new DM1 mechanism-based biochemical assay, we screened a collection of isolated natural compounds and a library of over 2100 extracts from plants and fungal strains. HPLC-based activity profiling in combination with spectroscopic methods were used to identify the active principles in the extracts. The bioactivity of the identified compounds was investigated in a human cell model and in a mouse model of DM1.We identified several alkaloids, including the -carboline harmine and the isoquinoline berberine, that ameliorated certain aspects of theDM1pathology in these models. Alkaloids as a compound class may have potential for drug discovery in other RNA-mediated diseases

An Evaluation of the Apparent Interdecadal Shift in the Tropical Divergent Circulation in the NCEP-NCAR Reanalysis

ABSTRACT Recent decadal regime shifts in the large-scale circulation of the tropical atmosphere are examined using analyses and independent observations of the circulation and precipitation. Comparisons between reanalysis products and independent observations suggest that the shifts that are apparent and significant in the reanalysis products may be artifacts of changes in the observing system and/or the data assimilation procedures

Suppression of HIV-Specific and Allogeneic T Cell Activation by Human Regulatory T Cells Is Dependent on the Strength of Signals

Regulatory T cells (Tregs) suppress immune responses against both self and non-self antigens. Tregs require activation through the T cell receptor (TCR) and IL-2 to exert their suppressive functions. However, how strength of TCR signals modulate the potency of Treg-mediated suppression of antigen-specific T cell activation remain unclear. We found that both strength of TCR signals and ratios of Tregs to target cells, either through superantigen, allogeneic antigens or HIV-specific peptides, modified the suppressive ability of Tregs. While human Tregs were able to mediate suppression in the presence of only autologous antigen-presenting cells, this was much less efficient as compared to when Tregs were activated by allogeneic dendritic cells. In another physiologically relevant system, we show that the strength of peptide stimulation, high frequency of responder CD8+ T cells or presence of high IL-2 can override the suppression of HIV-specific CD8+ T cells by Tregs. These findings suggest that ratios and TCR activation of human Tregs, are important parameters to overcome robust immune responses to pathogens or allogeneic antigens. Modulating the strength of T cell signals and selective enhancement or depletion of antigen-specific Tregs thus may have implications for designing potent vaccines and regulating immune responses during allogeneic transplantation and chronic infections

Resting Regulatory CD4 T Cells: A Site of HIV Persistence in Patients on Long-Term Effective Antiretroviral Therapy

BACKGROUND: In HIV-infected patients on long-term HAART, virus persistence in resting long-lived CD4 T cells is a major barrier to curing the infection. Cell quiescence, by favouring HIV latency, reduces the risk of recognition and cell destruction by cytotoxic lymphocytes. Several cell-activation-based approaches have been proposed to disrupt cell quiescence and then virus latency, but these approaches have not eradicated the virus. CD4+CD25+ regulatory T cells (Tregs) are a CD4+ T-cell subset with particular activation properties. We investigated the role of these cells in virus persistence in patients on long-term HAART. METHODOLOGY/PRINCIPAL FINDINGS: We found evidence of infection of resting Tregs (HLADR(-)CD69(-)CD25(hi)FoxP3+CD4+ T cells) purified from patients on prolonged HAART. HIV DNA harbouring cells appear more abundant in the Treg subset than in non-Tregs. The half-life of the Treg reservoir was estimated at 20 months. Since Tregs from patients on prolonged HAART showed hyporesponsiveness to cell activation and inhibition of HIV-specific cytotoxic T lymphocyte-related functions upon activation, therapeutics targeting cell quiescence to induce virus expression may not be appropriate for purging the Treg reservoir. CONCLUSIONS: Our results identify Tregs as a particular compartment within the latent reservoir that may require a specific approach for its purging

Casein kinase I δ/ɛ phosphorylates topoisomerase IIα at serine-1106 and modulates DNA cleavage activity

We previously reported that phosphorylation of topoisomerase (topo) IIα at serine-1106 (Ser-1106) regulates enzyme activity and sensitivity to topo II-targeted drugs. In this study we demonstrate that phosphorylation of Ser-1106, which is flanked by acidic amino acids, is regulated in vivo by casein kinase (CK) Iδ and/or CKIɛ, but not by CKII. The CKI inhibitors, CKI-7 and IC261, reduced Ser-1106 phosphorylation and decreased formation of etoposide-stabilized topo II–DNA cleavable complex. In contrast, the CKII inhibitor, 5,6-dichlorobenzimidazole riboside, did not affect etoposide-stabilized topo II–DNA cleavable complex formation. Since, IC261 specifically targets the Ca2+-regulated isozymes, CKIδ and CKIɛ, we examined the effect of down-regulating these enzymes on Ser-1106 phosphorylation. Down-regulation of these isozymes with targeted si-RNAs led to hypophosphorylation of the Ser-1106 containing peptide. However, si-RNA-mediated down-regulation of CKIIα and α′ did not alter Ser-1106 phosphorylation. Furthermore, reduced phosphorylation of Ser-1106, observed in HRR25 (CKIδ/ɛ homologous gene)-deleted Saccharomyces cerevisiae cells transformed with human topo IIα, was enhanced following expression of human CKIɛ. Down-regulation of CKIδ and CKIɛ also led to reduced formation of etoposide stabilized topo II–DNA cleavable complex. These results provide strong support for an essential role of CKIδ/ɛ in phosphorylating Ser-1106 in human topo IIα and in regulating enzyme function

The CLIVAR C20C Project: Which components of the Asian-Australian monsoon circulation variations are forced and reproducible?

A multi-model set of atmospheric simulations forced by historical sea surface temperature (SST) or SSTs plus Greenhouse gases and aerosol forcing agents for the period of 1950-1999 is studied to identify and understand which components of the Asian-Australian monsoon (A-AM) variability are forced and reproducible. The analysis focuses on the summertime monsoon circulations, comparing model results against the observations. The priority of different components of the A-AM circulations in terms of reproducibility is evaluated. Among the subsystems of the wide A-AM, the South Asian monsoon and the Australian monsoon circulations are better reproduced than the others, indicating they are forced and well modeled. The primary driving mechanism comes from the tropical Pacific. The western North Pacific monsoon circulation is also forced and well modeled except with a slightly lower reproducibility due to its delayed response to the eastern tropical Pacific forcing. The simultaneous driving comes from the western Pacific surrounding the maritime continent region. The Indian monsoon circulation has a moderate reproducibility, partly due to its weakened connection to June-July-August SSTs in the equatorial eastern Pacific in recent decades. Among the A-AM subsystems, the East Asian summer monsoon has the lowest reproducibility and is poorly modeled. This is mainly due to the failure of specifying historical SST in capturing the zonal land-sea thermal contrast change across the East Asia. The prescribed tropical Indian Ocean SST changes partly reproduce the meridional wind change over East Asia in several models. For all the A-AM subsystem circulation indices, generally the MME is always the best except for the Indian monsoon and East Asian monsoon circulation indices