Hippocampus specific iron deficiency alters competition and cooperation between developing memory systems

Iron deficiency (ID) is the most common gestational micronutrient deficiency in the world, targets the fetal hippocampus and striatum and results in long-term behavioral abnormalities. These structures primarily mediate spatial and procedural memory, respectively, in the rodent but have interconnections that result in competition or cooperation during cognitive tasks. We determined whether ID-induced impairment of one alters the function of the other by genetically inducing a 40% reduction of hippocampus iron content in late fetal life in mice and measuring dorsal striatal gene expression and metabolism and the behavioral balance between the two memory systems in adulthood. Slc11a2hipp/hipp mice had similar striatum iron content, but 18% lower glucose and 44% lower lactate levels, a 30% higher phosphocreatine:creatine ratio, and reduced iron transporter gene expression compared to wild type (WT) littermates, implying reduced striatal metabolic function. Slc11a2hipp/hipp mice had longer mean escape times on a cued task paradigm implying impaired procedural memory. Nevertheless, when hippocampal and striatal memory systems were placed in competition using a Morris Water Maze task that alternates spatial navigation and visual cued responses during training, and forces a choice between hippocampal and striatal strategies during probe trials, Slc11a2hipp/hipp mice used the hippocampus-dependent response less often (25%) and the visual cued response more often (75%) compared to WT littermates that used both strategies approximately equally. Hippocampal ID not only reduces spatial recognition memory performance but also affects systems that support procedural memory, suggesting an altered balance between memory systems

Transforming growth factor-β and breast cancer: Tumor promoting effects of transforming growth factor-β

The transforming growth factor (TGF)-βs are potent growth inhibitors of normal epithelial cells. In established tumor cell systems, however, the preponderant experimental evidence suggests that TGF-βs can foster tumor-host interactions that indirectly support the viability and/or progression of cancer cells. The timing of this 'TGF-β switch' during the progressive transformation of epithelial cells is not clear. More recent evidence also suggests that autocrine TGF-β signaling is operative in some tumor cells, and can also contribute to tumor invasiveness and metastases independent of an effect on nontumor cells. The dissociation of antiproliferative and matrix associated effects of autocrine TGF-β signaling at a transcriptional level provides for a mechanism(s) by which cancer cells can selectively use this signaling pathway for tumor progression. Data in support of the cellular and molecular mechanisms by which TGF-β signaling can accelerate the natural history of tumors will be reviewed in this section

Key signalling nodes in mammary gland development and cancer. Mitogen-activated protein kinase signalling in experimental models of breast cancer progression and in mammary gland development

Seven classes of mitogen-activated protein kinase (MAPK) intracellular signalling cascades exist, four of which are implicated in breast disease and function in mammary epithelial cells. These are the extracellular regulated kinase (ERK)1/2 pathway, the ERK5 pathway, the p38 pathway and the c-Jun N-terminal kinase (JNK) pathway. In some forms of human breast cancer and in many experimental models of breast cancer progression, signalling through the ERK1/2 pathway, in particular, has been implicated as being important. We review the influence of ERK1/2 activity on the organised three-dimensional association of mammary epithelial cells, and in models of breast cancer cell invasion. We assess the importance of epidermal growth factor receptor family signalling through ERK1/2 in models of breast cancer progression and the influence of ERK1/2 on its substrate, the oestrogen receptor, in this context. In parallel, we consider the importance of these MAPK-centred signalling cascades during the cycle of mammary gland development. Although less extensively studied, we highlight the instances of signalling through the p38, JNK and ERK5 pathways involved in breast cancer progression and mammary gland development

One thousand plant transcriptomes and the phylogenomics of green plants

Abstract: Green plants (Viridiplantae) include around 450,000–500,000 species1, 2 of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life

The relationship between quality of life and change in mobility 1 year postinjury in individuals with spinal cord injury

Riggins MS, Kankipati P, Oyster ML, Cooper RA, Boninger ML. The relationship between quality of life and change in mobility 1 year postinjury in individuals with spinal cord injury. Objective: To examine quality-of-life (QOL) factors and change in mobility in individuals with traumatic spinal cord injury (SCI) 1 year after injury. Design: Retrospective case study of National SCI Database data. Setting: SCI Model Systems (SCIMS) sites (N=18). Participants: Subjects (N=1826; age >18y) who presented to an SCIMS site after traumatic SCI between June 2004 and July 2009 and returned for 1-year follow-up. All subjects had FIM mobility data for both assessments. Interventions: Not applicable. Main Outcome Measures: Assessment of impairment based on Lower-Extremity Motor Score. Assessment of QOL based on Craig Handicap Assessment and Reporting Technique, Patient Health Questionnaire, Satisfaction With Life Scale, Self-perceived Health Status, and pain severity scores. Results: Of the sample, 55 individuals transitioned from walking to wheelchair use within 1 year of discharge. This group had the highest number of individuals from minority groups (52.8%) and the lowest employment rate (7.3%). Compared with individuals who transitioned from wheelchair use to walking or maintained wheelchair use or ambulation, the walking-to-wheelchair transition group had significantly lower QOL scores (P<.01), including higher depression (P<.01) and higher pain severity (P<.001). Conclusions: Individuals with SCI who transitioned from walking at discharge to wheelchair use within 1 year had low QOL factors, including high pain and depression scores. Rehabilitation professionals should consider encouraging marginal ambulators to work toward functional independence from a wheelchair, rather than primary ambulation during acute inpatient rehabilitation. © 2011 American Congress of Rehabilitation Medicine

Epigenetic lesions at the H19 locus in Wilms' tumour patients

To test the potential role of H19 as a tumour suppressor gene we have examined its expression and DNA methylation in Wilms\u27 tumours (WTs). In most WTs (18/25), H19 RNA was reduced at least 20–fold from fetal kidney levels. Of the expression–negative tumours ten retained 11p15.5 heterozygosity: in nine of these, H19 DNA was biallelically hypermethylated and in two cases hypermethylation locally restricted to H19 sequences was also present in the non–neoplastic kidney parenchyma. IGF2 mRNA was expressed in most but not all WTs and expression patterns were consistent with IGF2/H19 enhancer competition without obligate inverse coupling. These observations implicate genetic and epigenetic inactivation of H19 in Wilms\u27 tumorigenesis. © 1994 Nature Publishing Group

A spatial analysis of the expanding roles of nurses in general practice

<p>Abstract</p> <p>Background</p> <p>Changes to the workforce and organisation of general practice are occurring rapidly in response to the Australian health care reform agenda, and the changing nature of the medical profession. In particular, the last five years has seen the rapid introduction and expansion of a nursing workforce in Australian general practices. This potentially creates pressures on current infrastructure in general practice.</p> <p>Method</p> <p>This study used a mixed methods, ‘rapid appraisal’ approach involving observation, photographs, and interviews.</p> <p>Results</p> <p>Nurses utilise space differently to GPs, and this is part of the diversity they bring to the general practice environment. At the same time their roles are partly shaped by the ways space is constructed in general practices.</p> <p>Conclusion</p> <p>The fluidity of nursing roles in general practice suggests that nurses require a versatile space in which to maximize their role and contribution to the general practice team.</p