The rise and fall of Australian physical activity policy 1996 - 2006: a national review framed in an international context.
This paper provides an historical review of physical activity policy development in Australia for a period spanning a decade since the release of the US Surgeon General's Report on Physical Activity and Health in 1996 and including the 2004 WHO Global Strategy on Diet, Physical Activity and Health. Using our definition of 'HARDWIRED' policy criteria, this Australian review is compared with an international perspective of countries with established national physical activity policies and strategies (New Zealand, Canada, Brazil, Scotland, Switzerland, the Netherlands and Finland). Methods comprised a literature and policy review, audit of relevant web sites, document searches and surveys of international stakeholders. All these selected countries embraced multi-strategic policies and undertook monitoring of physical activity through national surveys. Few committed to policy of more than three years duration and none undertook systematic evaluation of national policy implementation. This Australian review highlights phases of innovation and leadership in physical activity-related policy, as well as periods of stagnation and decline; early efforts were amongst the best in the world but by the mid-point of this review (the year 2000), promising attempts towards development of a national intersectoral policy framework were thwarted by reforms in the Federal Sport and Recreation sector. Several well received reviews of evidence on good practices in physical activity and public health were produced in the period but leadership and resources were lacking to implement the policies and programs indicated. Latterly, widespread publicity and greatly increased public and political interest in chronic disease prevention, (especially in obesity and type 2 diabetes) have dominated the framework within which Australian policy deliberations have occurred. Finally, a national physical activity policy framework for the Health sector emerged, but not as a policy vision that was inclusive of the other essential sectors such as Education, Transport, Urban Planning as well as Sport and Recreation. Despite some progression of physical activity policy in the decade since 1995/6, this review found inconsistent policy development, both in Australia and elsewhere. Arguably, Australia has done no worse than other countries, but more effective responses to physical inactivity in populations can be built only on sustainable multi-sectoral public health policy partnerships that are well informed by evidence of effectiveness and good practice. In Australia and elsewhere prerequisites for success are political support, long-term investment and commitment to program implementation and evaluation. An urgent priority is media and political advocacy for physical activity focussed on these factors.


The sexually dimorphic adipose fin is an androgen target tissue in the brown trout (Salmo trutta fario).
An investigation has been described on the relationship of body length, age and sex with adipose fin length and the number of androgen receptor (AR)-containing cells in the adipose fin as a secondary sexual characteristic for brown trout (Salmo trutta fario). Firstly, body and adipose fin lengths of 2- to 5-year-old brown trout were measured. Thereafter, these fish were killed by decapitation, then their sexes were determined, and adipose fins were excised. The cellular bases of AR binding activities in the adipose fins were analyzed with an antibody against human/rat AR peptide. Immunocytochemistry and western blotting techniques were performed with this antibody. Analysis of morphological measurements indicated that body length and age had a linear relationship with adipose fin length. The coefficients of determination for the body length and age were 0.92 and 0.85 in the male fish and 0.76 and 0.73 in the female fish against the adipose fin length, respectively. At 2 years of age, cells in the adipose fin did not exhibit AR immunoreactivity. However, AR-immunopositive cells were abundant in the adipose fin of 3- to 5-year-old fish. Moreover, the number of AR-immunopositive cells was significantly (P < 0.05) high in males and increased with age. These observations indicate that the adipose fin in the brown trout is a probable target for androgen action and that tissue function or development may to some extent be androgen dependent. In addition, it is likely that such an effect will be mediated by specific androgen receptors.


Counterimmunoelectrophoresis in the detection of antibodies to Schistosoma japonicum.
Counterimmunoelectrophoresis (CIE) was used to detect antibodies to Schistosoma japonicum soluble egg antigen in 118 sera from people living in a schistosomiasis endemic area in the Philippines. The sera were also tested for antibodies by the circumoval precipitin test (COPT); 53% were found positive by CIE and 48% positive by COPT. No significant differences were found between the tests (P = 0.18 by McNemar's test). Cross-reactions with sera from patients with intestinal capillariasis and monkeys with experimental angiostrongyliasis were not found and no false reactions were detected with sera from "normal" controls. The CIE test as used in the present studies was found to be comparable to the COPT in sensitivity and specificity as related to cross-reactivity with sera from nematode infections such as intestinal capillariasis and angiostrongyliasis. Results are usually available quickly with nearly 70% of any reactions occurring within 1 h. The test should be of value in seroepidemiologic surveys in schistosomiasis-endemic areas.


The empirical basis of generalized anxiety disorder.
The authors review the empirical data on generalized anxiety disorder, a diagnostic category that has been among the more conceptually challenging in psychiatric nosology. Published studies and recent findings that were considered by the Generalized Anxiety Disorder Subcommittee of the DSM-IV Anxiety Disorders Work Group are reviewed. Among the issues examined are diagnostic reliability, comorbidity, boundaries with other disorders, and clinical features. A variety of data on the reliability and validity of generalized anxiety disorder have been produced. Some authors have suggested that generalized anxiety disorder is better conceptualized as a vulnerability that should be located on axis II, and others have recommended that the category be eliminated. Although the diagnostic reliability of generalized anxiety disorder is lower than that of other anxiety disorders, the features constituting the diagnostic criteria for generalized anxiety disorder have been found to be reliable. An important development has been the determination of a set of somatic symptoms associated with generalized anxiety disorder that differs substantially from those for other anxiety disorders. These findings led to reduction in the number of items in the symptom criterion, from 18 in DSM-III-R to six in DSM-IV. Another substantial revision is greater emphasis on the uncontrollability of worry. Whereas the data on construct and discriminant validity, age at onset, course, familial transmission, and response to treatment generally support the DSM-IV definition of generalized anxiety disorder, the construct continues to have weaknesses and further research is needed.


Defining the geographical range of the Plasmodium knowlesi reservoir.
The simian malaria parasite, Plasmodium knowlesi, can cause severe and fatal disease in humans yet it is rarely included in routine public health reporting systems for malaria and its geographical range is largely unknown. Because malaria caused by P. knowlesi is a truly neglected tropical disease, there are substantial obstacles to defining the geographical extent and risk of this disease. Information is required on the occurrence of human cases in different locations, on which non-human primates host this parasite and on which vectors are able to transmit it to humans. We undertook a systematic review and ranked the existing evidence, at a subnational spatial scale, to investigate the potential geographical range of the parasite reservoir capable of infecting humans. After reviewing the published literature we identified potential host and vector species and ranked these based on how informative they are for the presence of an infectious parasite reservoir, based on current evidence. We collated spatial data on parasite occurrence and the ranges of the identified host and vector species. The ranked spatial data allowed us to assign an evidence score to 475 subnational areas in 19 countries and we present the results on a map of the Southeast and South Asia region. We have ranked subnational areas within the potential disease range according to evidence for presence of a disease risk to humans, providing geographical evidence to support decisions on prevention, management and prophylaxis. This work also highlights the unknown risk status of large parts of the region. Within this unknown category, our map identifies which areas have most evidence for the potential to support an infectious reservoir and are therefore a priority for further investigation. Furthermore we identify geographical areas where further investigation of putative host and vector species would be highly informative for the region-wide assessment.


Lupus anticoagulant and anticardiolipin antibodies in young adults with cerebral ischemia.
Our study evaluates in an unselected young population with cerebral ischemia the frequency of antiphospholipid antibodies; the relationship of antiphospholipid antibodies to conventional risk factors for and pathological mechanisms of cerebral ischemia; and the risk of recurrence of cerebral ischemia or systemic thrombotic events in patients with antiphospholipid antibodies compared with those without. We prospectively tested for antiphospholipid antibodies in 55 of 59 young (aged 15-44 years) adults consecutively examined for ischemic stroke (n = 44) or transient ischemic attack (n = 11). These patients underwent a complete clinical and laboratory assessment for cerebral ischemia and had a 3-year mean follow-up. Ten patients (18%), all with stroke, had antiphospholipid antibodies. Antiphospholipid antibodies were significantly more frequent in women than in men (Fisher's test, p = 0.014). Two patients with antiphospholipid antibodies had a new diagnosis of systemic lupus erythematosus. On angiography, none of the patients with antiphospholipid antibodies had extracranial lesions. Patients with antiphospholipid antibodies had significantly more prior cerebral events (Fisher's test, p = 0.014), and, by survival analysis, higher probability of cerebral ischemic or systemic thrombotic events during follow-up than patients without (log rank test, p less than 0.005). We conclude that the prevalence of antiphospholipid antibodies is rather high in young adults with cerebral ischemia; that patients with cerebral ischemia and antiphospholipid antibodies may have unrecognized systemic lupus erythematosus; and that, among young patients with cerebral ischemia, patients with antiphospholipid antibodies constitute a subgroup at high risk of cerebral ischemic or systemic thrombotic recurrence. Prevention in this latter group may require close follow-up and treatment.


Prognostic Value of Microscopic Hematuria after Induction of Remission in Antineutrophil Cytoplasmic Antibodies-Associated Vasculitis.
Pauci-immune glomerulonephritis (PIGN) is a major prognostic factor in antineutrophil cytoplasmic antibodies-associated vasculitis (AAV). Renal remission is usually defined as improvement or stabilization of serum creatinine and proteinuria levels but the significance of hematuria is unclear. We evaluated the prognostic value of microscopic hematuria in patients in remission from a first flare of PIGN. A multicenter retrospective study was conducted of all patients with histologically proven PIGN in northern France who presented a first renal flare of AAV between 2003 and 2013. All patients received conventional induction treatment and were considered in remission. Two groups were defined by the presence (H+) or absence (H-) of hematuria (dipstick 1+ and/or cytology ≥10,000 erythrocytes/mL). The primary outcome measure was the occurrence of renal relapse (RR) and/or end-stage renal disease (ESRD). Eighty-six patients were included: 41 (48%) had hematuria at remission. The median follow-up time was 44 ± 34 months. There was no significant difference between the groups in terms of the primary endpoint or the number of RR. However, the survival rate without RR was significantly lower in the H+ group (p = 0.002). In multivariate analysis, risk factors for RR were hematuria at remission for relapses within 44 months (hazard ratio [HR] 4.15; 95% CI 1.15-15.01; p = 0.03) and the duration of maintenance immunosuppressive therapy (HR 0.96 per additional month; 95% CI 0.94-0.99; p = 0.002). Hematuria at remission after a first PIGN flare was not associated with ESRD but with the occurrence of RR within 44 months of remission.


The structure of the tau haplotype in controls and in progressive supranuclear palsy.
The group of neurodegenerative diseases collectively known as tauopathies are characterized by hallmark lesions consisting of fibrillar aggregates of the microtubule-associated protein, tau (MAPT). Mutations of the tau gene (MAPT) are the cause of frontotemporal dementia with parkinsonism linked to chromosome 17, giving tau a central role in the pathogenic process. The chromosomal region containing MAPT has been shown to evolve into two major haplotypes, H1 and H2, which are defined by linkage disequilibrium (LD) between several polymorphisms over the entire MAPT gene. Studies to date suggest a complete absence of recombination between these two haplotypes. The more common haplotype H1 is over-represented in patients with progressive supranuclear palsy (PSP) and corticobasal degeneration. Using single nucleotide polymorphisms, we mapped LD in the regions flanking MAPT and have established the maximum extent of the haplotype block on chromosome 17q21.31 as a region covering approximately 2 Mb. This gene-rich region extends centromerically beyond the corticotrophin releasing hormone receptor 1 gene (CRHR1) to a region of approximately 400 kb, where there is a complete loss of LD. The telomeric end is defined by an approximately 150 kb region just beyond the WNT3 gene. We show that the entire, fully extended H1 haplotype is associated with PSP, which implicates several other genes in addition to MAPT, as candidate pathogenic loci.


Adenosine stress native T1 mapping in severe aortic stenosis: evidence for a role of the intravascular compartment on myocardial T1 values.
Myocardial T1 relaxation times have been reported to be markedly abnormal in diverse myocardial pathologies, ascribed to interstitial changes, evaluated by T1 mapping and calculation of extracellular volume (ECV). T1 mapping is sensitive to myocardial water content of both intra- and extracellular in origin, but the effect of intravascular compartment changes on T1 has been largely neglected. We aimed to assess the role of intravascular compartment on native (pre-contrast) T1 values by studying the effect of adenosine-induced vasodilatation in patients with severe aortic stenosis (AS) before and after aortic valve replacement (AVR). 42 subjects (26 patients with severe AS without obstructive coronary artery disease and 16 controls) underwent cardiovascular magnetic resonance at 3 T for native T1-mapping (ShMOLLI), first-pass perfusion (myocardial perfusion reserve index-MPRI) at rest and during adenosine stress, and late gadolinium enhancement (LGE). AS patients had increased resting myocardial T1 (1196±47 ms vs. 1168±27 ms, p=0.037), reduced MPRI (0.92±0.31 vs. 1.74±0.32, p<0.001), and increased left ventricular mass index (LVMI) and LGE volume compared to controls. During adenosine stress, T1 in AS was similar to controls (1240±51 ms vs. 1238±54 ms, p=0.88), possibly reflecting a similar level of maximal coronary vasodilatation in both groups. Conversely, the T1 response to stress was blunted in AS (ΔT1 3.7±2.7% vs. 6.0±4.2% in controls, p=0.013). Seven months after AVR (n=16) myocardial T1 and response to adenosine stress recovered towards normal. Native T1 values correlated with reduced MPRI, aortic valve area, and increased LVMI. Our study suggests that native myocardial T1 values are not only influenced by interstitial and intracellular water changes, but also by changes in the intravascular compartment. Performing T1 mapping during or soon after vasodilator stress may affect ECV measurements given that hyperemia alone appears to substantially alter T1 values.


Microstructural Parameters for Modelling of Superconducting Foams.
Superconducting YBa2Cu3Oy (YBCO) foams were prepared using commercial open-cell, polyurethane foams as starting material to form ceramic Y2BaCuO5 foams which are then converted into superconducting YBCO by using the infiltration growth process. For modelling the superconducting and mechanical properties of the foam samples, a Kelvin-type cell may be employed as a first approach as reported in the literature for pure polyurethane foams. The results of a first modelling attempt in this direction are presented concerning an estimation of the possible trapped fields (TFs) and are compared to experimental results at 77 K. This simple modelling revealed already useful information concerning the best suited foam structure to realize large TF values, but it also became obvious that for various other parameters like magnetostriction, mechanical strength, percolative current flow and the details of the TF distribution, a refined model of a superconducting foam sample incorporating the real sample structure must be considered. Thus, a proper description of the specific microstructure of the superconducting YBCO foams is required. To obtain a set of reliable data, YBCO foam samples were investigated using optical microscopy, scanning electron microscopy and electron backscatter diffraction (EBSD). A variety of parameters including the size and shape of the cells and windows, the length and shape of the foam struts or ligaments and the respective intersection angles were determined to better describe the real foam structure. The investigation of the foam microstructures revealed not only the differences to the original polymer foams used as base material, but also provided further insights to the infiltration growth process via the large amount of internal surface in a foam sample.


Enhanced R-matrix algorithms for multilayered diffraction gratings.
I present enhanced R-matrix algorithms for analysis of general multilayered diffraction gratings. The previous R-matrix algorithms are enhanced in three aspects: computational efficiency, numerical stability, and application of half R-matrix in addition to full and quarter R-matrix recursions. On the basis of the eigensolutions of rigorous coupled-wave analysis, the enhanced R-matrix algorithms deal with eigen-submatrices directly and bypass the auxiliary layer R matrix. Such exclusion of a layer matrix leads to improvements in efficiency and algorithm robustness particularly for zero or small layer thickness relative to wavelength. Application of the enhanced algorithms to grating diffraction is exploited especially for the half and quarter R-matrix recursions. Comparison of various R-matrix algorithms via a table of flop counts shows that the enhanced algorithms are more efficient apart from being well conditioned.


Precision medicine in inflammatory bowel disease: concept, progress and challenges.
Crohn's disease and ulcerative colitis are increasingly prevalent, relapsing and remitting inflammatory bowel diseases (IBDs) with variable disease courses and complications. Their aetiology remains unclear but current evidence shows an increasingly complex pathophysiology broadly centring on the genome, exposome, microbiome and immunome. Our increased understanding of disease pathogenesis is providing an ever-expanding arsenal of therapeutic options, but these can be expensive and patients can lose response or never respond to certain therapies. Therefore, there is now a growing need to personalise therapies on the basis of the underlying disease biology and a desire to shift our approach from "reactive" management driven by disease complications to "proactive" care with an aim to prevent disease sequelae. Precision medicine is the tailoring of medical treatment to the individual patient, encompassing a multitude of data-driven (and multi-omic) approaches to foster accurate clinical decision-making. In IBD, precision medicine would have significant benefits, enabling timely therapy that is both effective and appropriate for the individual. In this review, we summarise some of the key areas of progress towards precision medicine, including predicting disease susceptibility and its course, personalising therapies in IBD and monitoring response to therapy. We also highlight some of the challenges to be overcome in order to deliver this approach.


Nanofabricated Ultraflexible Electrode Arrays for High-Density Intracortical Recording.
Understanding brain functions at the circuit level requires time-resolved simultaneous measurement of a large number of densely distributed neurons, which remains a great challenge for current neural technologies. In particular, penetrating neural electrodes allow for recording from individual neurons at high temporal resolution, but often have larger dimensions than the biological matrix, which induces significant damage to brain tissues and therefore precludes the high implant density that is necessary for mapping large neuronal populations with full coverage. Here, it is demonstrated that nanofabricated ultraflexible electrode arrays with cross-sectional areas as small as sub-10 µm2 can overcome this physical limitation. In a mouse model, it is shown that these electrodes record action potentials with high signal-to-noise ratio; their dense arrays allow spatial oversampling; and their multiprobe implantation allows for interprobe spacing at 60 µm without eliciting chronic neuronal degeneration. These results present the possibility of minimizing tissue displacement by implanted ultraflexible electrodes for scalable, high-density electrophysiological recording that is capable of complete neuronal circuitry mapping over chronic time scales.


Diversity and dynamics of a north atlantic coastal Vibrio community.
Vibrios are ubiquitous marine bacteria that have long served as models for heterotrophic processes and have received renewed attention because of the discovery of increasing numbers of facultatively pathogenic strains. Because the occurrence of specific vibrios has frequently been linked to the temperature, salinity, and nutrient status of water, we hypothesized that seasonal changes in coastal water bodies lead to distinct vibrio communities and sought to characterize their level of differentiation. A novel technique was used to quantify shifts in 16S rRNA gene abundance in samples from Barnegat Bay, N.J., collected over a 15-month period. Quantitative PCR (QPCR) with primers specific for the genus Vibrio was combined with separation and quantification of amplicons by constant denaturant capillary electrophoresis (CDCE). Vibrio populations identified by QPCR-CDCE varied between summer and winter samples, suggesting distinct warm-water and year-round populations. Identification of the CDCE populations by cloning and sequencing of 16S rRNA genes from two summer and two winter samples confirmed this distinction. It further showed that CDCE populations corresponded in most cases to approximately 98% rRNA similarity groups and suggested that the abundance of these follows temperature trends. Phylogenetic comparison yielded closely related cultured and often pathogenic representatives for most sequences, and the temperature ranges of these isolates confirmed the trends seen in the environmental samples. Overall, this suggests that temperature is a good predictor of the occurrence of closely related vibrios but that considerable microdiversity of unknown significance coexists within this trend.


Empirical assessment of state-and-transition models with a long-term vegetation record from the Sonoran Desert.
Resilience-based frameworks, including state-and-transition models (STM), are being increasingly called upon to inform policy and guide ecosystem management, particularly in rangelands. Yet, multiple challenges impede their effective implementation: (1) paucity of empirical tests of resilience concepts, such as alternative states and thresholds, and (2) heavy reliance on expert models, which are seldom tested against empirical data. We developed an analytical protocol to identify unique plant communities and their transitions, and applied it to a long-term vegetation record from the Sonoran Desert (1953-2009). We assessed whether empirical trends were consistent with resilience concepts, and evaluated how they may inform the construction and interpretation of expert STMs. Seven statistically distinct plant communities were identified based on the cover of 22 plant species in 68 permanent transects. We recorded 253 instances of community transitions, associated with changes in species composition between successive samplings. Expectedly, transitions were more frequent among proximate communities with similar species pools than among distant communities. But unexpectedly, communities and transitions were not strongly constrained by soil type and topography. Only 18 transitions featured disproportionately large compositional turnover (species dissimilarity ranged between 0.54 and 0.68), and these were closely associated with communities that were dominated by the common shrub (burroweed, Haplopappus tenuisecta); indicating that only some, and not all, communities may be prone to large compositional change. Temporal dynamics in individual transects illustrated four general trajectories: stability, nondirectional drift, reversibility, and directional shifts that were not reversed even after 2-3 decades. The frequency of transitions and the accompanying species dissimilarity were both positively correlated with fluctuation in precipitation, indicating that climatic drivers require more attention in STMs. Many features of the expert models, including the number of communities and participant species, were consistent with empirical trends, but expert models underrepresented recent increases in cacti while overemphasizing the introduced Lehmann's lovegrass (Eragrostis lehmanniana). Quantification of communities and transitions within long-term vegetation records presents several quantitative metrics such as transition frequency, magnitude of accompanying compositional change, presence of unidirectional trajectories, and lack of reversibility within various timescales, which can clarify resilience concepts and inform the construction and interpretation of STMs.


Photophysical properties of C60 colloids suspended in water with Triton X-100 surfactant: excited-state properties with femtosecond resolution.
We examine the photophysics of a colloidal suspension of C(60) particles in a micellar solution of Triton X-100 and water, prepared via a new synthesis which allows high-concentration suspensions. The particle sizes are characterized by transmission electron microscopy and dynamic light scattering and found to be somewhat polydisperse in the range of 10-100 nm. The suspension is characterized optically by UV-vis spectroscopy, femtosecond transient absorption spectroscopy, laser flash photolysis, and z-scan. The ground-state absorbance spectrum shows a broad absorbance feature centered near 450 nm which is indicative of colloidal C(60). The transient absorption dynamics, presented for the first time with femtosecond resolution, are very similar to that of thin films of C(60) and indicate a strong quenching of the singlet excited state on short time scales and evidence of little intersystem crossing to a triplet excited state. Laser flash photolysis reveals that a triplet excited-state absorption spectrum, which is essentially identical in shape to that of molecular C(60) solutions, does indeed arise, but with much lower magnitude and somewhat shorter lifetime. Z-scan analysis confirms that the optical response of this material is dominated by nonlinear scattering.


Disease-causing mutations in BEST1 gene are associated with altered sorting of bestrophin-1 protein.
Mutations in BEST1 gene, encoding the bestrophin-1 (Best1) protein are associated with macular dystrophies. Best1 is predominantly expressed in the retinal pigment epithelium (RPE), and is inserted in its basolateral membrane. We investigated the cellular localization in polarized MDCKII cells of disease-associated Best1 mutant proteins to study specific sorting motifs of Best1. Real-time PCR and western blots for endogenous expression of BEST1 in MDCK cells were performed. Best1 mutant constructs were generated using site-directed mutagenesis and transfected in MDCK cells. For protein sorting, confocal microscopy studies, biotinylation assays and statistical methods for quantification of mislocalization were used. Analysis of endogenous expression of BEST1 in MDCK cells revealed the presence of BEST1 transcript but no protein. Confocal microscopy and quantitative analyses indicate that transfected normal human Best1 displays a basolateral localization in MDCK cells, while cell sorting of several Best1 mutants (Y85H, Q96R, L100R, Y227N, Y227E) was altered. In contrast to constitutively active Y227E, constitutively inactive Y227F Best1 mutant localized basolaterally similar to the normal Best1 protein. Our data suggest that at least three basolateral sorting motifs might be implicated in proper Best1 basolateral localization. In addition, non-phosphorylated tyrosine 227 could play a role for basolateral delivery.


Predicting the behavior of techno-social systems.
We live in an increasingly interconnected world of techno-social systems, in which infrastructures composed of different technological layers are interoperating within the social component that drives their use and development. Examples are provided by the Internet, the World Wide Web, WiFi communication technologies, and transportation and mobility infrastructures. The multiscale nature and complexity of these networks are crucial features in understanding and managing the networks. The accessibility of new data and the advances in the theory and modeling of complex networks are providing an integrated framework that brings us closer to achieving true predictive power of the behavior of techno-social systems.


Two-dimensional morphogen gradient in Xenopus: boundary formation and real-time transduction response.
Morphogen gradients play an important role in pattern formation in embryo. However, the interpretation of position in a morphogen gradient is not well understood. Because it is hard to analyze morphogen gradients especially in opaque embryos such as those of Xenopus, it is necessary to fix and section the embryo, thereby eliminating the possibility of real-time observation, and making more difficult the interpretation of events that take place in three dimensions. We describe here a two-dimensional preparation of cells from a Xenopus blastula animal cap, in which an activin concentration gradient appears to be formed and interpreted at the same rate and in the same way as in normal embryos. We use two-dimensional preparations of this kind to contribute the following new information about gradient formation and interpretation in embryo. We determine the dynamics of formation of an activin activity gradient in real time. We demonstrate that this gradient is established by diffusion of activin through intercellular space and does not require internalization of receptor or ligand. We also show that the generation of a boundary of gene expression depends on the interpretation, rather than a change of composition, of the concentration gradient.


Photochromic materials: more than meets the eye.
Photochromic materials are a family of compounds which can undergo reversible photo-switches between two different states or isomers with remarkably different properties. Inspired by their smart photo-switchable characteristics, a variety of light-driven functional materials have been exploited, such as ultrahigh-density optical data storage, molecular switches, logic gates, molecular wires, optic/electronic devices, sensors, bio-imaging and so on. This review commences with a brief description of exciting progress in this field, from systems in solution to modified functional surfaces. Further development of these photo-switchable systems into practical applications as well as existing challenges are also discussed and put in prospect.


Anterior optic nerve capillary blood flow response to diurnal variation of mean ocular perfusion pressure in early untreated primary open-angle glaucoma.
To examine the impact of diurnal variation in intraocular pressure (IOP) and mean ocular perfusion pressure (MOPP) on the variation in anterior optic nerve capillary blood flow (BF) in patients with untreated early primary open-angle glaucoma (uPOAG) and healthy volunteers. Fourteen patients with uPOAG (age, 56.3 +/- 12 years [SD]; seven men) and 14 normal subjects (age, 57.6 +/- 9.9 years; five men) were examined. Diurnal IOP, systolic (SBP) and diastolic (DBP) blood pressures, and optic nerve head (ONH) topography were measured every hour; and diurnal BF was measured by flowmeter every 2 hours between 0700 and 2200 hours. A perfusion image analyzer was used to calculate the mean BF within the rim (mean rim flow, MRF). The local flow (LF) was calculated using the median and mean flow rates within a 10 x 10-pixel window placed on the rim in the area of maximum topography fluctuation (MTF). The MOPP was then calculated. Mixed-effect linear models were used to analyze the repeated measures data in which both fixed and random effects were included. IOP, BP, and MOPP had significant diurnal variation (P < 0.040). LF measured at the sector of MTF significantly changed in patients with uPOAG (P = 0.006) but not in normal subjects (P = 0.660). MRF did not show significant diurnal change in either group (P = 0.130, P = 0.770). LF increased significantly after lunch in the uPOAG group (P = 0.001). SBP had a significant effect on LF over the course of the day in the uPOAG group (P = 0.043). The diurnal change in IOP, BP, and MOPP did not have a significant effect on MTF in either group. In uPOAG, the local flow, in areas of greatest topographical change, correlated inversely with IOP at 0700 hours (P < or = 0.002). The mean rim flow did not change during the day, implying that the anterior optic nerve capillary blood flow was autoregulated in both normal subjects and in patients with uPOAG, despite significant changes in IOP and MOPP. However, the regions of greatest diurnal change in rim topography (MTF) had significant diurnal change in capillary blood flow in patients with uPOAG but not in normal subjects.


A cluster of mutations disrupt the avirulence but not the virulence function of AvrPto.
avrPto in Pseudomonas syringae pv. tomato encodes an avirulence protein that triggers race-specific resistance in tomato plants carrying Pto. The AvrPto protein is secreted from P. syringae pv. tomato to plant cells through the type III secretion pathway and activates race-specific resistance by a direct interaction with the Pto protein. Here we report that avrPto enhances the virulence of P. syringae pv. tomato in a strain-dependent manner in tomato plants lacking Pto. To determine whether the virulence function can be structurally separated from the avirulence function, we examined the virulence activity of a group of AvrPto mutants that carry single amino acid substitutions and lack the avirulence activity on tomato plants. Three mutants that were clustered in the center of AvrPto exhibited virulence activity in tomato plants with or without Pto. The rest of the mutations abolished the virulence. The identification of these mutants suggested that the avirulence function of AvrPto can be structurally separated from the virulence function.


Adverse Reactions Induced by Minocycline: A Review of Literature.
Minocycline is a tetracycline antibiotic that is widely used to treat infections and is a first-line oral antibiotic in the treatment of moderate to severe inflammatory acne. Although it has high efficacy, several adverse reactions, including life-threatening ones, have been reported in association with its use. To identify all the potential adverse reactions due to minocycline and analyze them in terms of the number of cases reported so far, salient features, severity and clinical outcome. Comprehensive PubMed search of English and non-English literature for case reports of adverse reactions to minocycline was conducted. A total of 550 cases were identified from over 200 publications. The major reported adverse events caused by minocycline are drug reaction with eosinophilia and systemic symptoms syndrome, autoimmune syndromes like hepatitis, lupus and vasculitis, acute eosinophilic pneumonia, pseudotumor cerebri, hyperpigmentation, serum sickness-like reaction, Sweet's syndrome and drug fever. Several other reactions involving multiple organ systems have also been reported. These show an overlap of clinical features and may be associated with multiple events causing considerable morbidity. Eight of these cases resulted in the death of the patients. In view of the evident potential of minocycline to cause long-lasting and severe adverse effects, significant morbidity and even mortality, it should be prescribed with caution in the first-line treatment for moderate to severe acne.