Paclitaxel-Induced Apoptosis Is BAK-Dependent, but BAX and BIM-Independent in Breast Tumor

Paclitaxel (Taxol)-induced cell death requires the intrinsic cell death pathway, but the specific participants and the precise mechanisms are poorly understood. Previous studies indicate that a BH3-only protein BIM (BCL-2 Interacting Mediator of cell death) plays a role in paclitaxel-induced apoptosis. We show here that BIM is dispensable in apoptosis with paclitaxel treatment using bim−/− MEFs (mouse embryonic fibroblasts), the bim−/− mouse breast tumor model, and shRNA-mediated down-regulation of BIM in human breast cancer cells. In contrast, both bak−/− MEFs and human breast cancer cells in which BAK was down-regulated by shRNA were more resistant to paclitaxel. However, paclitaxel sensitivity was not affected in bax−/−MEFs or in human breast cancer cells in which BAX was down-regulated, suggesting that paclitaxel-induced apoptosis is BAK-dependent, but BAX-independent. In human breast cancer cells, paclitaxel treatment resulted in MCL-1 degradation which was prevented by a proteasome inhibitor, MG132. A Cdk inhibitor, roscovitine, blocked paclitaxel-induced MCL-1 degradation and apoptosis, suggesting that Cdk activation at mitotic arrest could induce subsequent MCL-1 degradation in a proteasome-dependent manner. BAK was associated with MCL-1 in untreated cells and became activated in concert with loss of MCL-1 expression and its release from the complex. Our data suggest that BAK is the mediator of paclitaxel-induced apoptosis and could be an alternative target for overcoming paclitaxel resistance

Further evidence supporting a role for gs signal transduction in severe malaria pathogenesis.

With the functional demonstration of a role in erythrocyte invasion by Plasmodium falciparum parasites, implications in the aetiology of common conditions that prevail in individuals of African origin, and a wealth of pharmacological knowledge, the stimulatory G protein (Gs) signal transduction pathway presents an exciting target for anti-malarial drug intervention. Having previously demonstrated a role for the G-alpha-s gene, GNAS, in severe malaria disease, we sought to identify other important components of the Gs pathway. Using meta-analysis across case-control and family trio (affected child and parental controls) studies of severe malaria from The Gambia and Malawi, we sought evidence of association in six Gs pathway candidate genes: adenosine receptor 2A (ADORA2A) and 2B (ADORA2B), beta-adrenergic receptor kinase 1 (ADRBK1), adenylyl cyclase 9 (ADCY9), G protein beta subunit 3 (GNB3), and regulator of G protein signalling 2 (RGS2). Our study amassed a total of 2278 cases and 2364 controls. Allele-based models of association were investigated in all genes, and genotype and haplotype-based models were investigated where significant allelic associations were identified. Although no significant associations were observed in the other genes, several were identified in ADORA2A. The most significant association was observed at the rs9624472 locus, where the G allele (approximately 20% frequency) appeared to confer enhanced risk to severe malaria [OR = 1.22 (1.09-1.37); P = 0.001]. Further investigation of the ADORA2A gene region is required to validate the associations identified here, and to identify and functionally characterize the responsible causal variant(s). Our results provide further evidence supporting a role of the Gs signal transduction pathway in the regulation of severe malaria, and request further exploration of this pathway in future studies

The Iowa Homemaker vol.6, no.2

Table of Contents Dedication, page 1 Invitation to The House by Maybelle A. Payton, page 2 Dedication of the Home Economics Hall, page 3 Home Economics of Tomorrow by Anna E. Richardson, page 5 And Now Comes the Fulfillment by Joanna M. Hansen, page 6 Pioneering in Home Economics by Josephine McMullen, page 8 With the Iowa State Home Economics Association, page 6 The Past Decade in Home Economics at I. S. C., page 9 The Dean MacKay Auditorium by Thirza Hull, page 10 Division of Home Economics by Marcia E. Turner, page 11 ‘Twas Team Work That Did It, page 12 Omicron Nu by Cora B. Miller, page 13 Girls’ 4-H Clubs, page 14 With the Iowa State Home Economics Association, page 1

The Iowa Homemaker vol.7, no.6

The Place of the Child by Anna E. Richardson, page 1 Liver for My Hotspur by Jeanette Beyer McCay, page 2 Christmas Problems for the Home Economics Class by Marcia E. Turner, page 3 Taking the Drudgery Out of Ironing Day by Edith Carse, page 4 Home Life in Uruguay by Frances Thomas, page 5 Girls’ 4-H Page, page 6 Looking Ahead in the State Association by Vera L. Mintle, page 8 Do We Need Help in Household Buying? by Frances A. Sims, page 10 Who’s There and Where by Dr. Lillian B. Storms, page 1

Intensive care nurse-family engagement from a global perspective: A qualitative multi-site exploration

Background: Critical illness is distressing for families, and often results in negative effects on family health that influence a family\u27s ability to support their critically ill family member. Although recent attention has been directed at improving care and outcomes for families of critically ill patients, the manner in which nurses engage with families is not fully understood. Objectives: To describe nurses’ perceptions and practices of family engagement in adult intensive care units from a global perspective. Design: A qualitative-descriptive multi-site design using content analysis. Settings: The study was conducted in 26 intensive care units of 12 urban, metropolitan, academic medical centers in ten countries, spanning five continents. Participants: A total of 65 registered nurses (77% women, age of M = 39.5, SD = 11.4 years) participated. Most held intensive care certification (72%) and had worked on average 10 (SD = 9.6) years in the ICU. Methods: Semi-structured, individual interviews (M = 38.4 min, SD = 12.0) were held with ICU nurses at the hospital (94%) or their home using an interview guide. Qualitative interview data were analysed using inductive content analysis. Results: We found that nurse-family engagement was an ebb and flow of relational power that needed to be carefully negotiated and balanced, with nurses holding and often exerting more power than families. Constant fluctuations in nurses’ practices of engagement occurred in day-to-day practice from shift-to-shift and from nurse-to-nurse. Family engagement was dependent on individual nurses’ attitudes and perceptions of family, the patient\u27s condition, and workload. Lastly, family engagement was shaped by the ICU context, with team culture, collaborative relationships, unit structures and organizational resources either enabling or limiting nurses’ ability to engage with families. Conclusions: This global study provides an in-depth understanding of the way nurses engage with families in ICU and reflects many different cultures and health systems. We found that nurse-family engagement was marked by a shifting, yet often unequal power distribution in the nurse-family relationship, inconsistent nurse engagement practices, both of which resulted in variable family engagement in intensive care. Our research contributes a detailed description of engagement as practiced in the everyday delivery of health care. A more concentrated team effort, based on a shared culture and defined framework of family care is needed to ensure that families of critically ill persons are fully engaged in all aspects of intensive care

Joint care can outweigh costs of nonkin competition in communal breeders

Competition between offspring can greatly influence offspring fitness and parental investment decisions, especially in communal breeders where unrelated competitors have less incentive to concede resources. Given the potential for escalated conflict, it remains unclear what mechanisms facilitate the evolution of communal breeding among unrelated females. Resolving this question requires simultaneous consideration of offspring in noncommunal and communal nurseries, but such comparisons are missing. In the Seychelles warbler Acrocephalus sechellensis, we compare nestling pairs from communal nests (2 mothers) and noncommunal nests (1 mother) with singleton nestlings. Our results indicate that increased provisioning rate can act as a mechanism to mitigate the costs of offspring rivalry among nonkin. Increased provisioning in communal broods, as a consequence of having 2 female parents, mitigates any elevated costs of offspring rivalry among nonkin: per-capita provisioning and survival was equal in communal broods and singletons, but lower in noncommunal broods. Individual offspring costs were also more divergent in noncommunal broods, likely because resource limitation exacerbates differences in competitive ability between nestlings. It is typically assumed that offspring rivalry among nonkin will be more costly because offspring are not driven by kin selection to concede resources to their competitors. Our findings are correlational and require further corroboration, but may help explain the evolutionary maintenance of communal breeding by providing a mechanism by which communal breeders can avoid these costs

Canine \u3cem\u3eRD3\u3c/em\u3e Mutation Establishes Rod-Cone Dysplasia Type 2 (\u3cem\u3ercd2\u3c/em\u3e) as Ortholog of Human and Murine \u3cem\u3erd3\u3c/em\u3e

Rod-cone dysplasia type 2 (rcd2) is an autosomal recessive disorder that segregates in collie dogs. Linkage disequilibrium and meiotic linkage mapping were combined to take advantage of population structure within this breed and to fine map rcd2 to a 230-kb candidate region that included the gene C1orf36 responsible for human and murine rd3, and within which all affected dogs were homozygous for one haplotype. In one of three identified canine retinal RD3 splice variants, an insertion was found that cosegregates with rcd2 and is predicted to alter the last 61 codons of the normal open reading frame and further extend the open reading frame. Thus, combined meiotic linkage and LD mapping within a single canine breed can yield critical reduction of the disease interval when appropriate advantage is taken of within-breed population structure. This should permit a similar approach to tackle other hereditary traits that segregate in single closed populations

New species longevity record for the northern quahog (=hard clam), Mercenaria mercenaria

Author Posting. © National Shellfisheries Association, 2011. This article is posted here by permission of National Shellfisheries Association for personal use, not for redistribution. The definitive version was published in Journal of Shellfish Research 30 (2011): 35-38, doi:10.2983/035.030.0106.Twenty-two large shells (>90 mm shell height) from a sample of live collected hard shell clams, Mercenaria mercenaria, from Buzzards Bay, Woods Hole, Cape Cod, MA, were subjected to sclerochronological analysis. Annually resolved growth lines in the hinge region and margin of the shell were identified and counted; the age of the oldest clam shell was determined to be at least 106 y. This age represents a considerable increase in the known maximum life span for M. mercenaria, more than doubling the maximum recorded life span of the species (46 y). More than 85% of the clam shells aged had more than 46 annual increments, the previous known maximum life span for the species. In this article we present growth rate and growth performance indicators (the overall growth performance and phi prime) for this record-breaking population of M. mercenaria. Recently discovered models of aging require accurate age records and growth parameters for bivalve populations if they are to be utilized to their full potential.This work was supported by grants from the American Diabetes Association (to Z. U.), American Federation for Aging Research (to A. C.), the University of Oklahoma College of Medicine Alumni Association (to A. C.), the BBSRC (to C. A. R.),the National Institutes of Health (AT006526 and HL077256 to Z. U.; AG022873 and AG025063 to S. N. A.), and the DFG Cluster of Excellence ‘‘Future Ocean’’ (to E. P.)