Construction of an environmentally sustainable development on a modified coastal sand mined and landfill site-Part 2. Re-establishing the natural ecosystems on the reconstructed beach dunes

Mimicking natural processes lead to progressive colonization and stabilization of the reconstructed beach dune ecosystem, as part of the ecologically sustainable development of Magenta Shores, on the central coast of New South Wales, Australia. The retained and enhanced incipient dune formed the first line of storm defence. Placement of fibrous Leptospermum windrows allowed wind blown sand to form crests and swales parallel to the beach. Burial of Spinifex seed head in the moist sand layer achieved primary colonization of the reconstructed dune and development of a soil fungal hyphae network prior to introduction of secondary colonizing species. Monitoring stakes were used as roosts by birds, promoting re-introduction of native plant species requiring germination by digestive tract stimulation. Bush regeneration reduced competition from weeds, allowing native vegetation cover to succeed. On-going weeding and monitoring are essential at Magenta Shores until bitou bush is controlled for the entire length of beach. The reconstructed dunes provide enhanced protection from sand movement and storm bite, for built assets, remnant significant vegetation and sensitive estuarine ecosystems. © 2010 by the authors

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (Pless than or equal to0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35–16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04–12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23–4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer

Oral tolerance to cancer can be abrogated by T regulatory cell inhibition

Oral administration of tumour cells induces an immune hypo-responsiveness known as oral tolerance. We have previously shown that oral tolerance to a cancer is tumour antigen specific, non-cross-reactive and confers a tumour growth advantage. We investigated the utilisation of regulatory T cell (Treg) depletion on oral tolerance to a cancer and its ability to control tumour growth. Balb/C mice were gavage fed homogenised tumour tissue – JBS fibrosarcoma (to induce oral tolerance to a cancer), or PBS as control. Growth of subcutaneous JBS tumours were measured; splenic tissue excised and flow cytometry used to quantify and compare systemic Tregs and T effector (Teff) cell populations. Prior to and/or following tumour feeding, mice were intraperitoneally administered anti-CD25, to inactivate systemic Tregs, or given isotype antibody as a control. Mice which were orally tolerised prior to subcutaneous tumour induction, displayed significantly higher systemic Treg levels (14% vs 6%) and faster tumour growth rates than controls (p<0.05). Complete regression of tumours were only seen after Treg inactivation and occurred in all groups - this was not inhibited by tumour feeding. The cure rates for Treg inactivation were 60% during tolerisation, 75% during tumour growth and 100% during inactivation for both tolerisation and tumour growth. Depletion of Tregs gave rise to an increased number of Teff cells. Treg depletion post-tolerisation and post-tumour induction led to the complete regression of all tumours on tumour bearing mice. Oral administration of tumour tissue, confers a tumour growth advantage and is accompanied by an increase in systemic Treg levels. The administration of anti-CD25 Ab decreased Treg numbers and caused an increase in Teffs. Most notably Treg cell inhibition overcame established oral tolerance with consequent tumor regression, especially relevant to foregut cancers where oral tolerance is likely to be induced by the shedding of tumour tissue into the gut

Regional differences in lumbar spinal posture and the influence of low back pain

<p>Abstract</p> <p>Background</p> <p>Spinal posture is commonly a focus in the assessment and clinical management of low back pain (LBP) patients. However, the link between spinal posture and LBP is not fully understood. Recent evidence suggests that considering regional, rather than total lumbar spine posture is important. The purpose of this study was to determine; if there are regional differences in habitual lumbar spine posture and movement, and if these findings are influenced by LBP.</p> <p>Methods</p> <p>One hundred and seventy female undergraduate nursing students, with and without LBP, participated in this cross-sectional study. Lower lumbar (LLx), Upper lumbar (ULx) and total lumbar (TLx) spine angles were measured using an electromagnetic tracking system in static postures and across a range of functional tasks.</p> <p>Results</p> <p>Regional differences in lumbar posture and movement were found. Mean LLx posture did not correlate with ULx posture in sitting (r = 0.036, p = 0.638), but showed a moderate inverse correlation with ULx posture in usual standing (r = -0.505, p < 0.001). Regional differences in range of motion from reference postures in sitting and standing were evident. BMI accounted for regional differences found in all sitting and some standing measures. LBP was not associated with differences in regional lumbar spine angles or range of motion, with the exception of maximal backward bending range of motion (F = 5.18, p = 0.007).</p> <p>Conclusion</p> <p>This study supports the concept of regional differences within the lumbar spine during common postures and movements. Global lumbar spine kinematics do not reflect regional lumbar spine kinematics, which has implications for interpretation of measures of spinal posture, motion and loading. BMI influenced regional lumbar posture and movement, possibly representing adaptation due to load.</p

The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP). As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP.</p> <p>Methods</p> <p>This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1) CLBP patients with movement impairment (n = 15, MI group) randomized to conventional physiotherapy regime 2) fifteen CLBP patients with control impairment randomized to core stability group (CI group) and 3) fifteen healthy controls (HC).</p> <p>Results</p> <p>The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P < 0.05). The CI group showed significant improvements in Fx, Fz, and My variables (p < 0.013, p < 0.006, and p < 0.002 respectively with larger effect sizes: Hedges's g > 0.8) after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p < 0.001), the post intervention scores between groups were not found significant (p < 0.288). Twenty percentage absolute risk reduction in flare-up rates during intervention was found in CI group (95% CI: 0.69-0.98).</p> <p>Conclusions</p> <p>In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8) indicating changes in load transfer patterns during perturbation similar to HC group.</p> <p>Trial registration</p> <p>UTRN095032158-06012009423714</p

DNA replication stress restricts ribosomal DNA copy number

Ribosomal RNAs (rRNAs) in budding yeast are encoded by ~100–200 repeats of a 9.1kb sequence arranged in tandem on chromosome XII, the ribosomal DNA (rDNA) locus. Copy number of rDNA repeat units in eukaryotic cells is maintained far in excess of the requirement for ribosome biogenesis. Despite the importance of the repeats for both ribosomal and non-ribosomal functions, it is currently not known how “normal” copy number is determined or maintained. To identify essential genes involved in the maintenance of rDNA copy number, we developed a droplet digital PCR based assay to measure rDNA copy number in yeast and used it to screen a yeast conditional temperature-sensitive mutant collection of essential genes. Our screen revealed that low rDNA copy number is associated with compromised DNA replication. Further, subculturing yeast under two separate conditions of DNA replication stress selected for a contraction of the rDNA array independent of the replication fork blocking protein, Fob1. Interestingly, cells with a contracted array grew better than their counterparts with normal copy number under conditions of DNA replication stress. Our data indicate that DNA replication stresses select for a smaller rDNA array. We speculate that this liberates scarce replication factors for use by the rest of the genome, which in turn helps cells complete DNA replication and continue to propagate. Interestingly, tumors from mini chromosome maintenance 2 (MCM2)-deficient mice also show a loss of rDNA repeats. Our data suggest that a reduction in rDNA copy number may indicate a history of DNA replication stress, and that rDNA array size could serve as a diagnostic marker for replication stress. Taken together, these data begin to suggest the selective pressures that combine to yield a “normal” rDNA copy number

Glycogen Synthase Kinase (GSK) 3β phosphorylates and protects nuclear myosin 1c from proteasome-mediated degradation to activate rDNA transcription in early G1 cells

Nuclear myosin 1c (NM1) mediates RNA polymerase I (pol I) transcription activation and cell cycle progression by facilitating PCAF-mediated H3K9 acetylation, but the molecular mechanism by which NM1 is regulated remains unclear. Here, we report that at early G1 the glycogen synthase kinase (GSK) 3β phosphorylates and stabilizes NM1, allowing for NM1 association with the chromatin. Genomic analysis by ChIP-Seq showed that this mechanism occurs on the rDNA as active GSK3β selectively occupies the gene. ChIP assays and transmission electron microscopy in GSK3β-/- mouse embryonic fibroblasts indicated that at G1 rRNA synthesis is suppressed due to decreased H3K9 acetylation leading to a chromatin state incompatible with transcription. We found that GSK3β directly phosphorylates the endogenous NM1 on a single serine residue (Ser-1020) located within the NM1 C-terminus. In G1 this phosphorylation event stabilizes NM1 and prevents NM1 polyubiquitination by the E3 ligase UBR5 and proteasome-mediated degradation. We conclude that GSK3β-mediated phosphorylation of NM1 is required for pol I transcription activation

SPIRITS 16tn in NGC 3556: A Heavily Obscured and Low-luminosity Supernova at 8.8 Mpc

We present the discovery by the SPitzer InfraRed Intensive Transients Survey (SPIRITS) of a likely supernova (SN) in NGC 3556 (M108) at only 8.8 Mpc that was not detected by optical searches. A luminous infrared (IR) transient at M [4.5] = −16.7 mag (Vega), SPIRITS 16tn is coincident with a dust lane in the inclined, star-forming disk of the host. Using observations in the IR, optical, and radio, we attempt to determine the nature of this event. We estimate A V ≈ 8–9 mag of extinction, placing it among the three most highly obscured IR-discovered SNe. The [4.5] light curve declined at a rate of 0.013 mag day−1, and the [3.6]–[4.5] color increased from 0.7 to gsim1.0 mag by 184.7 days post discovery. Optical/IR spectroscopy shows a red continuum but no clearly discernible features, preventing a definitive spectroscopic classification. Radio observations constrain the radio luminosity of SPIRITS 16tn to L ν lesssim 1024 erg s−1 Hz−1 between 3 and 15 GHz, excluding many varieties of core-collapse SNe. An SN Ia is ruled out by the observed IR color and lack of spectroscopic features from Fe-peak elements. SPIRITS 16tn was fainter at [4.5] than typical stripped-envelope SNe by ≈1 mag. Comparison of the spectral energy distribution to SNe II suggests that SPIRITS 16tn was both highly obscured and intrinsically dim, possibly akin to the low-luminosity SN 2005cs. We infer the presence of an IR dust echo powered by an initial peak luminosity of the transient of 5 × 1040 erg s−1 lesssim L peak lesssim 4 × 1043 erg s−1, consistent with the observed range for SNe II. This discovery illustrates the power of IR surveys to overcome the compounding effects of visible extinction and optically subluminous events in completing the inventory of nearby SNe

Immunological analysis of a Lactococcus lactis-based DNA vaccine expressing HIV gp120

For reasons of efficiency Escherichia coli is used today as the microbial factory for production of plasmid DNA vaccines. To avoid hazardous antibiotic resistance genes and endotoxins from plasmid systems used nowadays, we have developed a system based on the food-grade Lactococcus lactis and a plasmid without antibiotic resistance genes. We compared the L. lactis system to a traditional one in E. coli using identical vaccine constructs encoding the gp120 of HIV-1. Transfection studies showed comparable gp120 expression levels using both vector systems. Intramuscular immunization of mice with L. lactis vectors developed comparable gp120 antibody titers as mice receiving E. coli vectors. In contrast, the induction of the cytolytic response was lower using the L. lactis vector. Inclusion of CpG motifs in the plasmids increased T-cell activation more when the E. coli rather than the L. lactis vector was used. This could be due to the different DNA content of the vector backbones. Interestingly, stimulation of splenocytes showed higher adjuvant effect of the L. lactis plasmid. The study suggests the developed L. lactis plasmid system as new alternative DNA vaccine system with improved safety features. The different immune inducing properties using similar gene expression units, but different vector backbones and production hosts give information of the adjuvant role of the silent plasmid backbone. The results also show that correlation between the in vitro adjuvanticity of plasmid DNA and its capacity to induce cellular and humoral immune responses in mice is not straight forward