A Mammalian Circadian Clock Model Incorporating Daytime Expression Elements

Models of the mammalian clock have traditionally been based around two feedback loops-the self-repression of Per/Cry by interfering with activation by BMAL/CLOCK, and the repression of Bmal/Clock by the REV-ERB proteins. Recent experimental evidence suggests that the D-box, a transcription factor binding site associated with daytime expression, plays a larger role in clock function than has previously been understood. We present a simplified clock model that highlights the role of the D-box and illustrate an approach for finding maximum-entropy ensembles of model parameters, given experimentally imposed constraints. Parameter variability can be mitigated using prior probability distributions derived from genome-wide studies of cellular kinetics. Our model reproduces predictions concerning the dual regulation of Cry1 by the D-box and Rev-ErbA/ROR response element (RRE) promoter elements and allows for ensemble-based predictions of phase response curves (PRCs). Nonphotic signals such as Neuropeptide Y (NPY) may act by promoting Cry1 expression, whereas photic signals likely act by stimulating expression from the E/E' box. Ensemble generation with parameter probability restraints reveals more about a model's behavior than a single optimal parameter set.

Rapid detection of TNT in aqueous media by selective label free surface enhanced Raman spectroscopy

We report rapid and ultra-sensitive detection system for 2,4,6-trinitrotoluene (TNT) using unmodified gold nanoparticles and surface-enhanced Raman spectroscopy (SERS). First, Meisenheimer complex has been formed in aqueous solution between TNT and cysteamine in less than 15 min of mixing. The complex formation is confirmed by the development of a pink colour and a new UV–vis absorption band around 520 nm. Second, the developed Meisenheimer complex is spontaneously self-assembled onto unmodified gold nanoparticles through a stable Au–S bond between the cysteamine moiety and the gold surface. The developed mono layer of cysteamine-TNT is then screened by SERS to detect and quantify TNT. Our experimental results demonstrate that the SERS-based assay provide an ultra-sensitive approach for the detection of TNT down to 22.7 ng/L. The unambiguous fingerprint identification of TNT by SERS represents a key advantage for our proposed method. The new method provides high selectivity towards TNT over 2,4 DNT and picric acid. Therefore it satisfies the practical requirements for the rapid screening of TNT in real life samples where the interim 24-h average allowable concentration of TNT in waste water is 0.04 mg/L.

Indian bank efficiency and productivity changes with undesirable outputs: A disaggregated approach

The objective of this study is to examine technical efficiency and productivity growth in the Indian banking sector over the period from 2004 to 2011. We apply an innovative methodological approach introduced by Chen et al. (2011) and Barros et al. (2012), who use a weighted Russell directional distance model to measure technical inefficiency. We further modify and extend that model to measure TFP change with NPLs. We find that the inefficiency levels are significantly different among the three ownership structure of banks in India. Foreign banks have strong market position in India and they pull the production frontier in a more efficient direction. SPBs and domestic private banks show considerably higher inefficiency. We conclude that the restructuring policy applied in the late 1990s and early 2000s by the Indian government has not had a long-lasting effect.

Mapping the regional influence of genetics on brain structure variability - A Tensor-Based Morphometry study

Genetic and environmental factors influence brain structure and function profoundly. The search for heritable anatomical features and their influencing genes would be accelerated with detailed 3D maps showing the degree to which brain morphometry is genetically determined. As part of an MRI study that will scan 1150 twins, we applied Tensor-Based Morphometry to compute morphometric differences in 23 pairs of identical twins and 23 pairs of same-sex fraternal twins (mean age: 23.8 ± 1.8 SD years). All 92 twins' 3D brain MRI scans were nonlinearly registered to a common space using a Riemannian fluid-based warping approach to compute volumetric differences across subjects. A multi-template method was used to improve volume quantification. Vector fields driving each subject's anatomy onto the common template were analyzed to create maps of local volumetric excesses and deficits relative to the standard template. Using a new structural equation modeling method, we computed the voxelwise proportion of variance in volumes attributable to additive (A) or dominant (D) genetic factors versus shared environmental (C) or unique environmental factors (E). The method was also applied to various anatomical regions of interest (ROIs). As hypothesized, the overall volumes of the brain, basal ganglia, thalamus, and each lobe were under strong genetic control; local white matter volumes were mostly controlled by common environment. After adjusting for individual differences in overall brain scale, genetic influences were still relatively high in the corpus callosum and in early-maturing brain regions such as the occipital lobes, while environmental influences were greater in frontal brain regions that have a more protracted maturational time-course.

Seasonal and spatial variations in rare earth elements to identify inter-aquifer linkages and recharge processes in an Australian catchment

With the aim of elucidating the seasonal behaviour of rare earth elements (REEs), surface and groundwaters were collected under dry and wet conditions in different hydrological units of the Teviot Brook catchment (Southeast Queensland, Australia). Sampled waters showed a large degree of variability in both REE abundance and normalised patterns. Overall REE abundance ranged over nearly three orders of magnitude, and was consistently lower in the sedimentary bedrock aquifer (18ppt<∑REE<477ppt) than in the other hydrological systems studied. Abundance was greater in springs draining rhyolitic rocks (∑REE=300 and 2054ppt) than in springs draining basalt ranges (∑REE=25 and 83ppt), yet was highly variable in the shallow alluvial groundwater (16ppt<∑REE<5294ppt) and, to a lesser extent, in streamwater (85ppt<∑REE<2198ppt). Generally, waters that interacted with different rock types had different REE patterns. In order to obtain an unbiased characterisation of REE patterns, the ratios between light and middle REEs (R(M/L)) and the ratios between middle and heavy REEs (R(H/M)) were calculated for each sample. The sedimentary bedrock aquifer waters had highly evolved patterns depleted in light REEs and enriched in middle and heavy REEs (0.17

P-n junction organic photovoltaics fabricated by all solution processing

We have prepared p-n junction organic photovoltaic cells using an all solution processing method with poly(3-hexylthiophene) (P3HT) as the donor and phenyl-C 61-butyric acid methyl ester (PCBM) as the acceptor. Interdigitated donor/acceptor interface morphology was observed in the device processed with the lowest boiling point solvent for PCBM used in this study. The influences of different solvents on donor/acceptor morphology and respective device performance were investigated simultaneously. The best device obtained had characteristically rough interface morphology with a peak to valley value ∼15 nm. The device displayed a power conversion efficiency of 1.78%, an open circuit voltage (V oc) 0.44 V, a short circuit current density (J sc) 9.4 mA/cm 2 and a fill factor 43%.

Examining signs of driver sleepiness, usage of sleepiness countermeasures and the associations with sleepy driving behaviours and individual factors

The impairing effect from sleepiness is a major contributor to road crashes. The ability of a sleepy driver to perceive their level of sleepiness is an important consideration for road safety as well as the type of sleepiness countermeasure used by drivers as some sleepiness countermeasures are more effective than others. The aims of the current study were to determine the extent that the signs of driver sleepiness were associated with sleepy driving behaviours, as well as determining which individual factors (demographic, work, driving, and sleep-related factors) were associated with using a roadside or in-vehicle sleepiness countermeasure. A sample of 1518 Australian drivers from the Australian State of New South Wales and the neighbouring Australian Capital Territory took part in the study. The participants’ experiences with the signs of sleepiness were reasonably extensive. A number of the early signs of sleepiness (e.g., yawning, frequent eye blinks) were related with continuing to drive while sleepy, with the more advanced signs of sleepiness (e.g., difficulty keeping eyes open, dreamlike state of consciousness) associated with having a sleep-related close call. The individual factors associated with using a roadside sleepiness countermeasure included age (being older), education (tertiary level), difficulties getting to sleep, not continuing to drive while sleepy, and having experienced many signs of sleepiness. The results suggest that these participants have a reasonable awareness and experience with the signs of driver sleepiness. Factors related to previous experiences with sleepiness were associated with implementing a roadside countermeasure. Nonetheless, the high proportions of drivers performing sleepy driving behaviours, suggest that concerted efforts are needed with road safety campaigns regarding the dangers of driving while sleepy.

Short-rib polydactyly and jeune syndromes are caused by mutations in WDR60

Short-rib polydactyly syndromes (SRPS I-V) are a group of lethal congenital disorders characterized by shortening of the ribs and long bones, polydactyly, and a range of extraskeletal phenotypes. A number of other disorders in this grouping, including Jeune and Ellis-van Creveld syndromes, have an overlapping but generally milder phenotype. Collectively, these short-rib dysplasias (with or without polydactyly) share a common underlying defect in primary cilium function and form a subset of the ciliopathy disease spectrum. By using whole-exome capture and massive parallel sequencing of DNA from an affected Australian individual with SRPS type III, we detected two novel heterozygous mutations in WDR60, a relatively uncharacterized gene. These mutations segregated appropriately in the unaffected parents and another affected family member, confirming compound heterozygosity, and both were predicted to have a damaging effect on the protein. Analysis of an additional 54 skeletal ciliopathy exomes identified compound heterozygous mutations in WDR60 in a Spanish individual with Jeune syndrome of relatively mild presentation. Of note, these two families share one novel WDR60 missense mutation, although haplotype analysis suggested no shared ancestry. We further show that WDR60 localizes at the base of the primary cilium in wild-type human chondrocytes, and analysis of fibroblasts from affected individuals revealed a defect in ciliogenesis and aberrant accumulation of the GLI2 transcription factor at the centrosome or basal body in the absence of an obvious axoneme. These findings show that WDR60 mutations can cause skeletal ciliopathies and suggest a role for WDR60 in ciliogenesis.

Chlamydial infections of fish: Diverse pathogens and emerging causes of disease in aquaculture species

Chlamydial infections of fish are emerging as an important cause of disease in new and established aquaculture industries. To date, epitheliocystis, a skin and gill disease associated with infection by these obligate intracellular pathogens, has been described in over 90 fish species, including hosts from marine and fresh water environments. Aided by advances in molecular detection and typing, recent years have seen an explosion in the description of these epitheliocystis-related chlamydial pathogens of fish, significantly broadening our knowledge of the genetic diversity of the order Chlamydiales. Remarkably, in most cases, it seems that each new piscine host studied has revealed the presence of a phylogenetically unique and novel chlamydial pathogen, providing researchers with a fascinating opportunity to understand the origin, evolution and adaptation of their traditional terrestrial chlamydial relatives. Despite the advances in this area, much still needs to be learnt about the epidemiology of chlamydial infections in fish if these pathogens are to be controlled in farmed environments. The lack of in vitro methods for culturing of chlamydial pathogens of fish is a major hindrance to this field. This review provides an update on our current knowledge of the taxonomy and diversity of chlamydial pathogens of fish, discusses the impact of these infections on the health, and highlights further areas of research required to understand the biology and epidemiology of this important emerging group of fish pathogens of aquaculture species.

Customised osteotomy guides and endoprosthetic reconstruction for periacetabular tumours

Purpose We sought to analyse clinical and oncological outcomes of patients after guided resection of periacetabular tumours and endoprosthetic reconstruction of the remaining defect. Methods From 1988 to 2008, we treated 56 consecutive patients (mean age 52.5 years, 41.1 % women). Patients were followed up either until death or February 2011 (mean follow up 5.5 years, range 0.1–22.5, standard deviation ± 5.3). Kaplan–Meier analysis was used to estimate survival rates. Results Disease-specific survival was 59.9 % at five years and 49.7 % at ten and 20 years, respectively. Wide resection margins were achieved in 38 patients, whereas 11 patients underwent marginal and seven intralesional resection. Survival was significantly better in patients with wide or marginal resection than in patients with intralesional resection (p = 0.022). Survival for patients with secondary tumours was significantly worse than for patients with primary tumours (p = 0.003). In 29 patients (51.8 %), at least one reoperation was necessary, resulting in a revision-free survival of 50.5 % at five years, 41.1 % at ten years and 30.6 % at 20 years. Implant survival was 77.0 % at five years, 68.6 % at ten years and 51.8 % at 20 years. A total of 35 patients (62.5 %) experienced one or more complications after surgery. Ten of 56 patients (17.9 %) experienced local recurrence after a mean of 8.9 months. The mean postoperative Musculoskeletal Tumor Society (MSTS) score was 18.1 (60.1 %). Conclusion The surgical approach assessed in this study simplifies the process of tumour resection and prosthesis implantation and leads to acceptable clinical and oncological outcomes.

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: A Mendelian randomisation analysis

Background To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. Methods We created a genetic score combining the effects of alleles of two common variants (rs6743376 and rs1542176) that are located upstream of IL1RN, the gene encoding the IL-1 receptor antagonist (IL-1Ra; an endogenous inhibitor of both IL-1α and IL-1β); both alleles increase soluble IL-1Ra protein concentration. We compared effects on inflammation biomarkers of this genetic score with those of anakinra, the recombinant form of IL-1Ra, which has previously been studied in randomised trials of rheumatoid arthritis and other inflammatory disorders. In primary analyses, we investigated the score in relation to rheumatoid arthritis and four cardiometabolic diseases (type 2 diabetes, coronary heart disease, ischaemic stroke, and abdominal aortic aneurysm; 453 411 total participants). In exploratory analyses, we studied the relation of the score to many disease traits and to 24 other disorders of proposed relevance to IL-1 signalling (746 171 total participants). Findings For each IL1RN minor allele inherited, serum concentrations of IL-1Ra increased by 0·22 SD (95% CI 0·18–0·25; 12·5%; p=9·3 × 10−33), concentrations of interleukin 6 decreased by 0·02 SD (−0·04 to −0·01; −1·7%; p=3·5 × 10−3), and concentrations of C-reactive protein decreased by 0·03 SD (−0·04 to −0·02; −3·4%; p=7·7 × 10−14). We noted the effects of the genetic score on these inflammation biomarkers to be directionally concordant with those of anakinra. The allele count of the genetic score had roughly log-linear, dose-dependent associations with both IL-1Ra concentration and risk of coronary heart disease. For people who carried four IL-1Ra-raising alleles, the odds ratio for coronary heart disease was 1·15 (1·08–1·22; p=1·8 × 10−6) compared with people who carried no IL-1Ra-raising alleles; the per-allele odds ratio for coronary heart disease was 1·03 (1·02–1·04; p=3·9 × 10−10). Per-allele odds ratios were 0·97 (0·95–0·99; p=9·9 × 10−4) for rheumatoid arthritis, 0·99 (0·97–1·01; p=0·47) for type 2 diabetes, 1·00 (0·98–1·02; p=0·92) for ischaemic stroke, and 1·08 (1·04–1·12; p=1·8 × 10−5) for abdominal aortic aneurysm. In exploratory analyses, we observed per-allele increases in concentrations of proatherogenic lipids, including LDL-cholesterol, but no clear evidence of association for blood pressure, glycaemic traits, or any of the 24 other disorders studied. Modelling suggested that the observed increase in LDL-cholesterol could account for about a third of the association observed between the genetic score and increased coronary risk. Interpretation Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. The cardiovascular risk might, in part, be mediated through an increase in proatherogenic lipid concentrations. Funding UK Medical Research Council, British Heart Foundation, UK National Institute for Health Research, National Institute for Health Research Cambridge Biomedical Research Centre, European Research Council, and European Commission Framework Programme 7.

Proton spin lattice relaxation in lithium ammonium sulphate LiNH4SO4

Lithium ammonium sulphate (LAS) undergoes a phase transition at TC1=459.5K from a paraelectric phase (phase I) to a ferroelectric phase (phase II) and again at TC2=283K to a polar ferroelastic phase (phase III). Proton spin lattice relaxation time measured at 10 MHz in powdered LAS in the temperature range 480 to 77K shows discontinuous changes at the two transitions.

Recovery and succession in a multi-species tropical seagrass meadow following experimental disturbance: the role of sexual and asexual reproduction

Recolonisation and succession in a multi-species tropical seagrass meadow was examined by creating gaps (50×50 cm) in the meadow and manipulating the supply of sexual and asexual propagules. Measurements of leaf shoot density and estimates of above-ground biomass were conducted monthly to measure recovery of gaps between September 1995 and November 1997. Measurements of the seeds stored in the sediment (seed bank) and horizontal rhizome growth of colonising species were also conducted to determine their role in the recovery process. Asexual colonisation through horizontal rhizome growth from the surrounding meadow was the main mechanism for colonisation of gaps created in the meadow. The seed bank played no role in recolonisation of cleared plots. Total shoot density and above-ground biomass (all species pooled) of cleared plots recovered asexually to the level of the undisturbed controls in 10 and 7 months, respectively. There was some sexual recruitment into cleared plots where asexual colonisation was prevented but seagrass abundance (shoot density and biomass) did not reach the level of unmanipulated controls. Seagrass species did not appear to form seed banks despite some species being capable of producing long-lived seeds. The species composition of cleared plots remained different to the undisturbed controls throughout the 26-month experiment. Syringodium isoetifolium was a rapid asexual coloniser of disturbed plots and remained at higher abundances than in the control treatments for the duration of the study. S. isoetifolium had the fastest horizontal rhizome growth of species asexually colonising cleared plots (6.9 mm day−1). Halophila ovalis was the most successful sexual coloniser but was displaced by asexually colonising species. H. ovalis was the only species observed to produce fruits during the study. Small disturbances in the meadow led to long-term (>2 years) changes in community composition. This study demonstrated that succession in tropical seagrass communities was not a deterministic process. Variations in recovery observed for different tropical seagrass communities highlighted the importance of understanding life history characteristics of species within individual communities to effectively predict their response to disturbance. A reproductive strategy involving clonal growth and production of long-lived, locally dispersed seeds is suggested which may provide an evolutionary advantage to plants growing in tropical environments subject to temporally unpredictable major disturbances such as cyclones

Fishery biology and management of Protonibea diacanthus (Sciaenidae) aggregations in far Northern Cape York Peninsula waters

The sciaenid Protonibea diacanthus is a large, long-lived predatory fish of inshore northern Australian waters, which forms annual aggregations that are fished extensively by traditional (subsistence) and recreational fishers. There are now widespread concerns that the resource is being overexploited. Indigenous fishers of the Cape York Northern Peninsula Area (NPA) relate that large adult fish (up to 1500 mm total length (TL)) made up the bulk of the catch from the sciaenid aggregations until about 1994. In contrast, sexually mature P. diacanthus comprised only a small component (12 fish out of 270=4.4%) examined in a 1999–2000 sampling programme that was biased towards the largest individuals available. At 790 mm TL, the minimum size at first maturity for female P. diacanthus in this study is much smaller than the 920 mm TL reported previously in Queensland waters. Developing ovaries were observed in specimens sampled from sciaenid aggregations which formed in NPA waters between May and September 2000. However, no fish with ripe or spent gonads were found in the study, so the current timing and location of the spawning season for P. diacanthus in the region remain unknown. Food items observed in the analysis of the diet of P. diacanthus from the NPA included a variety of teleosts and invertebrates. The range of animal taxa represented in the prey items support the description of an ‘opportunistic predator’ attributed to the species. In our sampling, the stomach contents of fish caught during the time of the aggregation events did not differ from those observed at other times of the year. A total of 114 P. diacanthus were tagged and released at aggregation sites during the study period, and 3 fish (2.6%) were subsequently recaptured. The low rate of tag returns from the wild stock tagging programme, both in this study (2.6%) and from recreational fisher tag/release programmes for the sciaenid elsewhere in Queensland (6.5%), were not explained by tag loss nor mortality, given the high retention rate of tags and the zero mortality seen in tank trials. In response to the biological findings from this study, indigenous community councils of the NPA imposed a 2-year fishing moratorium for P. diacanthus. Surveys at aggregation sites in 2002 and 2003 established that much larger fish (mean size 103.5 cm TL) were again present on the grounds, albeit in very low numbers. These recent preliminary results highlight the critical need for continued monitoring and management of the P. diacanthus fishery in the NPA, if prospects for resource recovery are to be realised. The NPA initiative has provided a rare opportunity to negotiate a co-management strategy, based on scientific data and traditional knowledge, for the recovery of a cultural and economically significant fished resource.

Productivity and health effects of anaplasmosis and babesiosis on Bos indicus cattle and their crosses, and the effects of differing intensity of tick control in Australia

Tick fever is an important disease of cattle where Rhipicephalus (Boophilus) microplus acts as a vector for the three causal organisms Babesia bovis, Babesia bigemina and Anaplasma marginale. Bos indicus cattle and their crosses are more resistant to the clinical effects of infection with B. bovis and B. bigemina than are Bos taurus cattle. Resistance is not complete, however, and herds of B. indicus-cross cattle are still at risk of babesiosis in environments where exposure to B. bovis is light in most years but occasionally high. The susceptibility of B. indicus cattle and their crosses to infection with A. marginale is similar to that of B. taurus cattle. In herds of B. indicus cattle and their crosses the infection rate of Babesia spp. and A. marginale is lowered because fewer ticks are likely to attach per day due to reduced numbers of ticks in the field (long-term effect on population, arising from high host resistance) and because a smaller proportion of ticks that do develop to feed on infected cattle will in turn be infected (due to lower parasitaemia). As a consequence, herds of B. indicus cattle are less likely than herds of B. taurus cattle to have high levels of population immunity to babesiosis or anaplasmosis. The effects of acaricide application on the probability of clinical disease due to anaplasmosis and babesiosis are unpredictable and dependent on the prevalence of infection in ticks and in cattle at the time of application. Attempting to manipulate population immunity through the toleration of specific threshold numbers of ticks with the aim of controlling tick fever is not reliable and the justification for acaricide application should be for the control of ticks rather than for tick fever. Vaccination of B. indicus cattle and their crosses is advisable in all areas where ticks exist, although vaccination against B. bigemina is probably not essential in pure B. indicus animals.