Dimethyl 2,2`-[(4-oxo-2-phenyl-4H-chromene-5,7-diyl)dioxy]diacetate:a less densely packed polymorph

The title molecule, C21H18O8, crystallizes in two crystal polymorphs,see also Nallasivam, Nethaji, Vembu & Jaswant [Acta Cryst. (2009),E65, o312-o313]. The main difference between the two polymorphs is in the conformation of the oxomethylacetate groups with regard to the almost planar [total puckering amplitude 0.047 (2) angstrom] chromene ring. In the title compound, the best planes of the oxomethylacetate groups through the non-H atoms are almost perpendicular to the chromene ring [making dihedral angles of 89.61 (6) and 80.59 (5)degrees], while in the second polymorph the molecules are close to planar. Both crystal structures are stabilized by C-H center dot center dot center dot O.

Hydroclimatic influence of large-scale circulation on the variability of reservoir inflow

In this study, the nature of basin-scale hydroclimatic association for Indian subcontinent is investigated. It is found that, the large-scale circulation information from Indian Ocean is also equally important in addition to the El Nino-Southern Oscillation (ENSO), owing to the geographical location of Indian subcontinent. The hydroclimatic association of the variation of monsoon inflow into the Hirakud reservoir in India is investigated using ENSO and EQUatorial INdian Ocean Oscillation (EQUINOO, the atmospheric part of Indian Ocean Dipole mode) as the large-scale circulation information from tropical Pacific Ocean and Indian Ocean regions respectively. Individual associations of ENSO & EQUINOO indices with inflow into Hirakud reservoir are also assessed and found to be weak. However, the association of inflows into Hirakud reservoir with the composite index (CI) of ENSO and EQUINOO is quite strong. Thus, the large-scale circulation information from Indian Ocean is also important apart form the ENSO. The potential of the combined information of ENSO and EQUINOO for predicting the inflows during monsoon is also investigated with promising results. The results of this study will be helpful to water resources managers due to fact that the nature of monsoon inflow is becoming available as an early prediction.

The Effects of Nicotine on the Regulation of Neuronal Alpha7 Nicotinic Acetylcholine Receptors and Intracellular Signalling Pathways

Nicotine, the addictive compound of tobacco products, exerts its effects in the brain by binding to neuronal acetylcholine nicotinic receptors (nAChRs). The aim of the present study was to increase the knowledge of nicotine s complex effects, the focus being on homomeric alpha7-nAChRs that are widely expressed in the brain. Nicotinic regulation of differential signalling molecules including transcriptional regulators was also studied. We found that the number of alpha7-nAChRs is increased in specific brain regions in mice, in a time-dependent manner after chronic oral nicotine administration. Our results suggest that in addition to alpha4beta2-nAChRs, the other major nAChR subtype expressed in the brain, the number of alpha7-nAChRs is affected by chronic presence of nicotine. We suggest that when studying the long-term effects of nicotine, the duration on administration is of great importance. Next, we observed that nicotine exposure induces accumulation of cAMP in cell cultures expressing nAChRs. Furthermore, nicotine-induced alpha7-nAChR upregulation was potentiated by treatments enhancing cAMP-signalling, suggesting a role for cAMP in the upregulation process. Protein kinase C (PKC) was found essential for the basal regulation of alpha7-nAChR number. The nicotine-evoked alpha7-nAChR upregulation could be further increased by PKC overexpression. Thirdly, the effects of nicotine on dopamine and cAMP regulated phosphoprotein (DARPP-32) were characterised in rat brain. The results show that DARPP-32 is regulated by both acute and long-term nicotine treatment in the striatal subdivisions. The effect of acute nicotine is dose-dependent and the three striatal regions display differential sensitivities to nicotine. Chronic nicotine is also able to regulate DARPP-32 signalling with prominent effect seen in the nucleus accumbens (NAc), suggesting a role for DARPP-32 in the mediation of long-term effects of nicotine. Finally, the regulation of transcription factors Elk-1 and FosB/deltaFosB by nicotine was investigated. We found that Elk-1 is activated by acute nicotine selectively in the NAc core and hippocampal area CA1, whereas acute nicotine does not affect FosB/deltaFosB. Long-term intermittent or continuous nicotine increases the level of total Elk-1 in the same brain regions as acute nicotine. FosB/deltaFosB is also affected by chronic nicotine. Thus, similarly to other drugs of abuse, nicotine regulates transcriptional regulators Elk-1 and FosB/deltaFosB. These results bring further support for a common mechanism underlying the development of addiction. Nicotine s positive effects on learning and memory might involve the transcription factor Elk-1 based on the changes seen in the hippocampus, the key area in cognitive functions.

Paracrine action of sFLT-1 secreted by stably-transfected Ehrlich ascites tumor cells and therapy using sFLT-1 inhibits ascites tumor growth in vivo

Background Vascular endothelial growth factor (VEGF) is known to play a major role in angiogenesis. A soluble form of Flt-1, a VEGF receptor, is potentially useful as an antagonist of VEGF, and accumulating evidence suggests the applicability of sFlt-1 in tumor suppression. In the present study, we have developed and tested strategies targeted specifically to VEGF for the treatment of ascites formation.Methods As an initial strategy, we produced recombinant sFLT-1 in the baculovirus expression system and used it as a trap to sequester VEGF in the murine ascites carcinoma model. The effect of the treatment on the weight of the animal, cell number, ascites volume and proliferating endothelial cells was studied. The second strategy involved, producing Ehrlich ascites tumor (EAT) cells stably transfected with vectors carrying cDNA encoding truncated form of Flt-1 and using these cells to inhibit ascites tumors in a nude mouse model. Results The sFLT-1 produced by the baculovirus system showed potent antiangiogenic activity as assessed by rat cornea and tube formation assay. sFLT-1 treatment resulted in reduced peritoneal angiogenesis with a concomitant decrease in tumor cell number, volume of ascites, amount of free VEGF and the number of invasive tumor cells as assayed by CD31 staining. EAT cells stably transfected with truncated form of Flt-1 also effectively reduced the tumor burden in nude mice transplanted with these cells, and demonstrated a reduction in ascites formation and peritoneal angiogenesis. Conclusions The inhibition of peritoneal angiogenesis and tumor growth by sequestering VEGF with either sFlt-1 gene expression by recombinant EAT cells or by direct sFLT-1 protein therapy is shown to comprise a potential therapy. Copyright (C) 2009 John Wiley & Sons, Ltd.

Drosophila melanogaster mounts a unique immune response to the rhabdovirus Sigma virus

Rhabdoviruses are important pathogens of humans, livestock, and plants that are often vectored by insects. Rhabdovirus particles have a characteristic bullet shape with a lipid envelope and surface-exposed transmembrane glycoproteins. Sigma virus (SIGMAV) is a member of the Rhabdoviridae and is a naturally occurring disease agent of Drosophila melanogaster. The infection is maintained in Drosophila populations through vertical transmission via germ cells. We report here the nature of the Drosophila innate immune response to SIGMAV infection as revealed by quantitative reverse transcription-PCR analysis of differentially expressed genes identified by microarray analysis. We have also compared and contrasted the immune response of the host with respect to two nonenveloped viruses, Drosophila C virus (DCV) and Drosophila X virus (DXV). We determined that SIGMAV infection upregulates expression of the peptidoglycan receptor protein genes PGRP-SB1 and PGRP-SD and the antimicrobial peptide (AMP) genes Diptericin-A, Attacin-A, Attacin-B, Cecropin-A1, and Drosocin. SIGMAV infection did not induce PGRP-SA and the AMP genes Drosomycin-B, Metchnikowin, and Defensin that are upregulated in DCV and/or DXV infections. Expression levels of the Toll and Imd signaling cascade genes are not significantly altered by SIGMAV infection. These results highlight shared and unique aspects of the Drosophila immune response to the three viruses and may shed light on the nature of the interaction with the host and the evolution of these associations.

Overcoming Barriers to People of Color in Union Leadership

[Excerpt] It has been 10 years since the report on full participation. In preparation for the 2005 AFL-CIO Convention, the AFL-CIO, under the direction of the Executive Council’s Civil and Human Rights Committee, initiated a study to consider what other steps can be taken to address the underrepresentation of people of color in union leadership. It is hoped that this report will serve as a complement to a similar report on working women that was submitted to the Executive Council by the Executive Council’s Working Women’s Committee in March 2004, entitled, “Overcoming Barriers to Women in Organizing and Leadership.”

Central America: Labor Reports and Child Labor Reports Pursuant to the Trade Act of 2002, Section 2102(c)(8)-(9)

[Excerpt] These comments are in response to the “Request for Information Concerning Labor Rights in Costa Rica, El Salvador, Guatemala, Honduras and Nicaragua and their Laws Governing Exploitative Child Labor” published at 68 Fed. Reg. 19580 (April 21, 2003). This Request for Information was issued pursuant to Section 2102(c)(8) and (9) of the Trade Act of 2002, Pub. L. 107-210, which requires the President, with respect to any proposed trade agreement, to submit to Congress a “meaningful labor rights report” and a “report describing the extent to which the country or countries that are parties to the agreement have in effect laws governing exploitative child labor.”

Ask a Working Woman Survey 2002

[Excerpt] On the job and in public policy, working women want changes that will strengthen families and build respect for work. Working women are deeply and increasingly concerned about health care and retirement security, as well as equal pay and equal opportunity. Concern about health care has surged in the past year. These are among the findings of the Ask a Working Woman Survey 2002, conducted for the AFL-CIO by Lake Snell Perry & Associates. This survey is the third in a series designed to examine the pressures faced by working women and the solutions they seek in their workplaces and through legislation. This report is part of a yearlong national project that included a field survey of nearly 20,000 working women across the country, from which the quotes appearing in this report are taken.

The Eligibility Definition Used in the Social Security Administration’s Disability Programs Needs to be Changed

In its October 2003 report on the definition of disability used by the Social Security Administration’s (SSA’s) disability programs [i.e., Social Security Disability Insurance (SSDI) and Supplemental Security Income (SSI) for people with disabilities], the Social Security Advisory Board raises the issue of whether this definition is at odds with the concept of disability embodied in the Americans with Disabilities Act (ADA) and, more importantly, with the aspirations of people with disabilities to be full participants in mainstream social activities and lead fulfilling, productive lives. The Board declares that “the Nation must face up to the contradictions created by the existing definition of disability.” I wholeheartedly agree. Further, I have concluded that we have to make fundamental, conceptual changes to both how we define eligibility for economic security benefits, and how we provide those benefits, if we are ever to fulfill the promise of the ADA. To convince you of that proposition, I will begin by relating a number of facts that paint a very bleak picture – a picture of deterioration in the economic security of the population that the disability programs are intended to serve; a picture of programs that purport to provide economic security, but are themselves financially insecure and subject to cycles of expansion and cuts that undermine their purpose; a picture of programs that are facing their biggest expenditure crisis ever; and a picture of an eligibility determination process that is inefficient and inequitable -- one that rations benefits by imposing high application costs on applicants in an arbitrary fashion. I will then argue that the fundamental reason for this bleak picture is the conceptual definition of eligibility that these programs use – one rooted in a disability paradigm that social scientists, people with disabilities, and, to a substantial extent, the public have rejected as being flawed, most emphatically through the passage of the ADA. Current law requires eligibility rules to be based on the premise that disability is medically determinable. That’s wrong because, as the ADA recognizes, a person’s environment matters. I will further argue that programs relying on this eligibility definition must inevitably: reward people if they do not try to help themselves, but not if they do; push the people they serve out of society’s mainstream, fostering a culture of isolation and dependency; relegate many to a lifetime of poverty; and undermine their promise of economic security because of the periodic “reforms” that are necessary to maintain taxpayer support. I conclude by pointing out that to change the conceptual definition for program eligibility, we also must change our whole approach to providing for the economic security of people with disabilities. We need to replace our current “caretaker” approach with one that emphasizes helping people with disabilities help themselves. I will briefly describe features that such a program might require, and point out the most significant challenges we would face in making the transition.