A systematic scoping review of the sustainability of vertical farming, plant-based alternatives, food delivery services and blockchain in food systems.
Food system technologies (FSTs) are being developed to accelerate the transformation towards sustainable food systems. Here we conducted a systematic scoping review that accounts for multiple dimensions of sustainability to describe the extent, range and nature of peer-reviewed literature that assesses the sustainability performance of four FSTs: plant-based alternatives, vertical farming, food deliveries and blockchain technology. Included literature had a dominant focus on environmental sustainability and less on public health and socio-economic sustainability. Gaps in the literature include empirical assessments on the sustainability of blockchain technology, plant-based seafood alternatives, public health consequences of food deliveries and socio-economic consequences of vertical farming. The development of a holistic sustainability assessment framework that demonstrates the impact of deploying FSTs is needed to guide investments in and the development of sustainable food innovation.


Degeneration of the cerebellar granule cell layer in transgenic mice expressing genes of human foamy virus.
Transgenic mice expressing various combinations of structural and regulatory genes of human foamy virus (HFV) develop a neurodegenerative syndrome. delta gpe transgenic mice (which express the auxiliary bel-1 and bet genes along with truncated forms of gag, pol, and env) develop a severe neurological syndrome consisting mainly of spastic tetraparesis and blindness, and show neuronal loss in the hippocampus and cerebral cortex. In addition, mice in two of eight delta gpe lines developed an ataxic gait. Here we studied the phenotype of these two lines, and show that these mice exhibit progressive degeneration of their cerebellar granule cells beginning at 4-8 weeks of age. Transgenic mRNA and HFV proteins accumulate in cerebellar granule cells immediately before the onset of degeneration. The Purkinje cell layer is largely unaffected by this pathological process. Probably due to the loss of granule cell processes, the cerebellar molecular layer is narrowed in the late stages of the disease. These findings indicate that HFV gene products can be neurotoxic for cerebellar granule cells.


Can a Quantum Walk Tell Which Is Which?A Study of Quantum Walk-Based Graph Similarity.
We consider the problem of measuring the similarity between two graphs using continuous-time quantum walks and comparing their time-evolution by means of the quantum Jensen-Shannon divergence. Contrary to previous works that focused solely on undirected graphs, here we consider the case of both directed and undirected graphs. We also consider the use of alternative Hamiltonians as well as the possibility of integrating additional node-level topological information into the proposed framework. We set up a graph classification task and we provide empirical evidence that: (1) our similarity measure can effectively incorporate the edge directionality information, leading to a significant improvement in classification accuracy; (2) the choice of the quantum walk Hamiltonian does not have a significant effect on the classification accuracy; (3) the addition of node-level topological information improves the classification accuracy in some but not all cases. We also theoretically prove that under certain constraints, the proposed similarity measure is positive definite and thus a valid kernel measure. Finally, we describe a fully quantum procedure to compute the kernel.


d -Limonene sensitizes docetaxel-induced cytotoxicity in human prostate cancer cells: Generation of reactive oxygen species and induction of apoptosis.
Clinical trials have shown that docetaxel combined with other novel agents can improve the survival of androgen-independent prostate cancer patients. d -Limonene, a non-nutrient dietary component, has been found to inhibit various cancer cell growths without toxicity. We sought to characterize whether a non-toxic dose of d -limonene may enhance tumor response to docetaxel in an in vitro model of metastatic prostate cancer. Human prostate carcinoma DU-145 and normal prostate epithelial PZ-HPV-7 cells were treated with various concentrations of d -limonene, docetaxel or a combination of both, and cell viability was determined by MTT assay. Intracellular reactive oxygen species (ROS), reduced glutathione (GSH) and caspase activity were measured. Apoptosis and apoptosis-related proteins were studied by enzyme-linked immunosorbent assay and Western blotting, respectively. d -Limonene and docetaxel in combination significantly enhanced the cytotoxicity to DU-145 cells than PZ-HPV-7 cells. Exposure of DU-145 cells to a combined d -limonene and docetaxel resulted in higher ROS generation, depletion of GSH, accompanied by increased caspase activity than docetaxel alone. It also triggered a series of effects involving cytochrome c , cleavages of caspase-9, 3 and poly (ADP-ribose) polymerase, and a shift in Bad:Bcl-xL ratio in favor of apoptosis. Apoptotic effect was significantly blocked on pretreatment with N -acetylcystein, indicating that antitumor effect is initiated by ROS generation, and caspase cascades contribute to the cell death. Our results show, for the first time, that d -limonene enhanced the antitumor effect of docetaxel against prostate cancer cells without being toxic to normal prostate epithelial cells. The combined beneficial effect could be through the modulation of proteins involved in mitochondrial pathway of apoptosis. d -Limonene could be used as a potent non-toxic agent to improve the treatment outcome of hormone-refractory prostate cancer with docetaxel.


A numerical wave-optical approach for the simulation of analyzer-based x-ray imaging.
An advanced wave-optical approach for simulating a monochromator-analyzer set-up in Bragg geometry with high accuracy is presented. The polychromaticity of the incident wave on the monochromator is accounted for by using a distribution of incoherent point sources along the surface of the crystal. The resulting diffracted amplitude is modified by the sample and can be well represented by a scalar representation of the optical field where the limitations of the usual 'weak object' approximation are removed. The subsequent diffraction mechanism on the analyzer is described by the convolution of the incoming wave with the Green-Riemann function of the analyzer. The free space propagation up to the detector position is well reproduced by a classical Fresnel-Kirchhoff integral. The preliminary results of this innovative approach show an excellent agreement with experimental data.


Epicardial adipose tissue thickness and ablation outcome of atrial fibrillation.
Epicardial fat was closely related to atrial fibrillation (AF). Transthoracic echocardiography (TTE) has been proposed to be a convenient imaging tool in assessing epicardial adipose tissue (EAT). The goal of the present study was to investigate whether the EAT thickness measured on TTE was a useful parameter in predicting procedural outcomes of AF ablations. A total of 227 paroxysmal AF (PAF) and 56 non-paroxysmal AF (non-PAF) patients receiving catheter ablations from 2008-2010 were enrolled. Echocardiography-derived regional EAT thickness from parasternal long-axis view was quantified for each patient. Free of recurrence was defined as the absence of atrial arrhythmias without using antiarrhythmic agents after ablations. The mean EAT thickness of the study population was 6.1 ± 0.8 mm. Non-PAF patients had a thicker EAT than that of PAF patients (7.0 ± 0.7 mm versus 5.9 ± 0.7 mm, p value <0.001). During the follow-up of 16 ± 9 months, there were 95 patients (33.6%) suffering from recurrences of atrial arrhythmias. Non-PAF, chads2 score, left atrial diameter and EAT thickness were independent predictors of recurrence after catheter ablations. At a cutoff value of 6 mm for PAF and 6.9 mm for non-PAF, the measurement of EAT thickness could help us to identify patients at risk of recurrences. EAT thickness may serve as a useful parameter in predicting recurrences after AF ablations. Compared to other imaging modalities, TTE can be an alternative choice with less cost and time in assessing the effects of EAT on ablation outcomes.


STC: A Simple to Complex Framework for Weakly-Supervised Semantic Segmentation.
Recently, significant improvement has been made on semantic object segmentation due to the development of deep convolutional neural networks (DCNNs). Training such a DCNN usually relies on a large number of images with pixel-level segmentation masks, and annotating these images is very costly in terms of both finance and human effort. In this paper, we propose a simple to complex (STC) framework in which only image-level annotations are utilized to learn DCNNs for semantic segmentation. Specifically, we first train an initial segmentation network called Initial-DCNN with the saliency maps of simple images (i.e., those with a single category of major object(s) and clean background). These saliency maps can be automatically obtained by existing bottom-up salient object detection techniques, where no supervision information is needed. Then, a better network called Enhanced-DCNN is learned with supervision from the predicted segmentation masks of simple images based on the Initial-DCNN as well as the image-level annotations. Finally, more pixel-level segmentation masks of complex images (two or more categories of objects with cluttered background), which are inferred by using Enhanced-DCNN and image-level annotations, are utilized as the supervision information to learn the Powerful-DCNN for semantic segmentation. Our method utilizes 40K simple images from Flickr.com and 10K complex images from PASCAL VOC for step-wisely boosting the segmentation network. Extensive experimental results on PASCAL VOC 2012 segmentation benchmark well demonstrate the superiority of the proposed STC framework compared with other state-of-the-arts.


Timing of follow-up after abnormal screening and diagnostic mammograms.
To evaluate woman-level characteristics associated with timing of follow-up after abnormal mammograms in an integrated healthcare system with an active breast health program. Retrospective cohort study. The study included women aged 40-84 years who had an abnormal mammogram (20,060 screening and 3184 diagnostic) recommended for follow-up. We compared characteristics of women who received any follow-up evaluation within <7, 8 to 14, 15 to 21, and 22 to 180 days. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariate ordinal logistic regression. The proportion of women seeking care within 7 days was 23% for screening and 69% for diagnostic mammograms. Characteristics associated with later follow-up (>8 days vs <7 days) after an abnormal screening mammogram included being older (OR=1.15; 95% CI, 1.04-1.26 [age 70-79 years]; OR=1.31; 95% CI, 1.14-1.51 [age 80+ years]), Asian (OR=1.18; 95% CI, 1.04-1.33), or having a college degree (OR=1.10; 95% CI, 1.01-1.19). Characteristics associated with earlier follow-up included family history of breast cancer (OR=0.93; 95% CI, 0.88-0.98), symptoms at time of mammogram (OR=0.79; 95% CI, 0.70-0.88), or extremely dense breasts (OR=0.82; 95% CI, 0.69-0.96). For diagnostic mammograms, symptoms at time of mammogram (OR=0.47; 95% CI, 0.39-0.56) and being obese (OR=0.79; 95% CI, 0.65-0.98) were associated with earlier follow-up. Several woman-level characteristics were associated with timely follow-up after an abnormal screening exam, but only presence of symptoms and being obese was associated with timely follow-up after an abnormal diagnostic exam.


Declining male births in Germany before and after reunification.
Male births occur 3% in excess of female births in mammals in a ratio (M/F) of 0.515. Many factors have been shown to influence this, including socioeconomic deprivation. This paper reviews live birth data for Germany over the period 1946-2009, and identifies secular trends in M/F pre- and post-reunification. The null hypothesis is that there were no differences between East and West Germany, geographically or temporally, before and after reunification. Annual data on male and female live births were obtained from the Human Mortality Database and analyzed with contingency tables. These data were available separately for East and West Germany (1950-1989). There was a significant decline in M/F in both German Republics overall and before reunification (p<0.0001). No decline was present after. Pre-reunification, West Germany had a lower overall M/F than East Germany (p=0.001). In conclusion, a declining M/F has been shown in many countries over the past decades. The two German Republics' M/F fell prior to reunification and the economic collapse of East Germany. Contracting societies that offer poor socioeconomic conditions (such as the communist former East Germany) may result in a decrease in M/F, but this is not reflected in the data, which show that M/F in West Germany prior to reunification was lower than in East Germany. This is not explicable with the contracting economies hypothesis; other and as yet unknown influences may have modified M/F trends anticipated by known variables.


How to recruit the injured lung.
Alveolar recruitment represents a challenging issue in ALI/ARDS patients. Multiple techniques have been compared: intermittent sighs, sustained application of high pressure in single or multiple episodes, use of progressive higher PEEP and lower tidal volumes (VT), with a fixed upper limit, and increase of PEEP, without modifying VT. Encouraging results emerge also from the use of prone position, that allows a better distribution of transalveolar forces, thus reducing ventilator induced lung injury. Moreover the use of spontaneous breathing, such as Bi-PAP mode, enhances re-expansion of dorsal lung regions and intriguing, but still uncertain results derive from biological variability of ventilatory pattern. Finally, a pressure-volume (P-V) curve of respiratory system can be employed to set appropriate PEEP level, to prevent collapse of new recruited alveoli. To monitor alveolar recruitment we can use P-V curves, continuous intra-arterial gas analysis, electrical impedence tomography. It is worth noting that different recruiting techniques are characterised by different efficacy and adverse hemodynamic effects. In conclusion, The "Open lung" approach should not be applied to every patient; it should be reserved to restore lung volume if deterioration occurs, by means of adequate PEEP level and lowest acceptable FiO(2).


The Relation between Perceived Social Support and Anxiety in Patients under Hemodialysis.
The increase in the number of patients under hemodialysis treatment is a universal problem. With regard to the fact that there have been few social-psychological studies conducted on patients under hemodialysis treatment, the current study was conducted to investigate anxiety and perceived social support and the relation between them among these patients. This cross-sectional study was conducted on 126 patients under hemodialysis treatment in Isfahan in 2012. After randomly selecting a hospital with a hemodialysis ward, purposive sampling was conducted. Data collection tools included state-trait anxiety and perceived social support inventory. The data were analyzed using the Spearman correlation coefficient. Among the participants, 68.3% received average perceived social support. In addition, perceiving the tangible dimension of support was lower compared to other dimensions (Mean 40.02). Level of trait and state anxiety (65 and 67.5%) of over half of the participants was average. There was in inverse relationship between state and trait anxiety and total perceived social support and emotional and information dimensions (r = -0.340, r = -0.229). State and trait anxiety had the highest relation with emotional and information dimension of social support, respectively. Patients under hemodialysis treatment suffer from numerous psychological and social problems. Low awareness and emotional problems result in the increase of anxiety and reduction of perceived social support. Reduction of social support has negative effect on treatment outcomes.


Can Bayesian models play a role in dental caries epidemiology? Evidence from an application to the BELCAP data set.
The aim of this study was to show the potential of Bayesian analysis in statistical modelling of dental caries data. Because of the bounded nature of the dmft (DMFT) index, zero-inflated binomial (ZIB) and beta-binomial (ZIBB) models were considered. The effects of incorporating prior information available about the parameters of models were also shown. The data set used in this study was the Belo Horizonte Caries Prevention (BELCAP) study (Böhning et al. (1999)), consisting of five variables collected among 797 Brazilian school children designed to evaluate four programmes for reducing caries. Only the eight primary molar teeth were considered in the data set. A data augmentation algorithm was used for estimation. Firstly, noninformative priors were used to express our lack of knowledge about the regression parameters. Secondly, prior information about the probability of being a structural zero dmft and the probability of being caries affected in the subpopulation of susceptible children was incorporated. With noninformative priors, the best fitting model was the ZIBB. Education (OR = 0.76, 95% CrI: 0.59, 0.99), all interventions (OR = 0.46, 95% CrI: 0.35, 0.62), rinsing (OR = 0.61, 95% CrI: 0.47, 0.80) and hygiene (OR = 0.65, 95% CrI: 0.49, 0.86) were demonstrated to be factors protecting children from being caries affected. Being male increased the probability of being caries diseased (OR = 1.19, 95% CrI: 1.01, 1.42). However, after incorporating informative priors, ZIB models' estimates were not influenced, while ZIBB models reduced deviance and confirmed the association with all interventions and rinsing only. In our application, Bayesian estimates showed a similar accuracy and precision than likelihood-based estimates, although they offered many computational advantages and the possibility of expressing all forms of uncertainty in terms of probability. The overdispersion parameter could expound why the introduction of prior information had significant effects on the parameters of the ZIBB model, while ZIB estimates remained unchanged. Finally, the best performance of ZIBB compared to the ZIB model was shown to catch overdispersion in data.


Do as I say: contradicting beliefs and attitudes towards sports concussion in Australia.
The objective of this study was to explore beliefs and attitudes of students studying exercise science in Australia towards sports concussion. A secondary objective explored differences between gender and previous experience of concussion. A total of 312 participants (m = 217; f = 95) responded to a series of statements ranging across a number of areas including personal attitudes and beliefs towards concussion: if they would risk playing with a concussion; their views on elite/professional athletes who continue to play after a concussion; and attitudes towards rehabilitation. Overall, attitudes revealed that it was not safe to play with a concussion, and it was believed that those who have had repeated concussions would be likely to suffer problems later in life. However, responses also indicated that they would risk playing with a concussion, and admired elite athletes who continued to play. When controlling for gender and previous concussions, males and those who sustained a previous concussion/s were more likely to continue playing. Conversely, females were more likely to complete rehabilitation prior to returning to sport. This study demonstrates in an Australian student cohort studying for a career in exercise and sports science, disparity between beliefs and attitudes regarding sports concussion.


Potent rewarding and reinforcing effects of the synthetic cathinone 3,4-methylenedioxypyrovalerone (MDPV).
Reports of abuse and toxic effects of synthetic cathinones, frequently sold as 'bath salts' or 'legal highs', have increased dramatically in recent years. One of the most widely used synthetic cathinones is 3,4-methylenedioxypyrovalerone (MDPV). The current study evaluated the abuse potential of MDPV by assessing its ability to support intravenous self-administration and to lower thresholds for intracranial self-stimulation (ICSS) in rats. In the first experiment, the rats were trained to intravenously self-administer MDPV in daily 2-hour sessions for 10 days at doses of 0.05, 0.1 or 0.2 mg/kg per infusion. The rats were then allowed to self-administer MDPV under a progressive ratio (PR) schedule of reinforcement. Next, the rats self-administered MDPV for an additional 10 days under short access (ShA; 2 hours/day) or long access (LgA; 6 hours/day) conditions to assess escalation of intake. A separate group of rats underwent the same procedures, with the exception of self-administering methamphetamine (0.05 mg/kg per infusion) instead of MDPV. In the second experiment, the effects of MDPV on ICSS thresholds following acute administration (0.1, 0.5, 1 and 2 mg/kg, i.p.) were assessed. MDPV maintained self-administration across all doses tested. A positive relationship between MDPV dose and breakpoints for reinforcement under PR conditions was observed. LgA conditions led to escalation of drug intake at 0.1 and 0.2 mg/kg doses, and rats self-administering methamphetamine showed similar patterns of escalation. Finally, MDPV significantly lowered ICSS thresholds at all doses tested. Together, these findings indicate that MDPV has reinforcing properties and activates brain reward circuitry, suggesting a potential for abuse and addiction in humans.


Reporting clinical research: guidance to encourage accurate and transparent research reporting.
To encourage accurate, complete, and transparent reporting of research studies we provide a brief overview of generic guidelines for reporting the main types of clinical research: randomised trials, observational studies in epidemiology, and systematic reviews. These and many other guidelines developed to help authors to achieve the highest standards in their research publications are available on the EQUATOR (Enhancing the Quality and Transparency of Health Research) Network website (www.equator-network.org).


Size and demography pattern of the domestic dog population in Bhutan: Implications for dog population management and disease control.
Understanding the demography of domestic dogs is essential to plan the dog population management and rabies control program. In this study, we estimated the owned and stray dog population and the proportion of owned dogs that are free-roaming in Bhutan. For this, a cross-sectional household surveys were conducted in six districts (both urban and rural areas) and two border towns in southern Bhutan. The population estimation was done by extrapolation of the mean number of dogs per household and dogs per person, whilst mark-resight survey was conducted to estimate the proportion of owned dogs that were free-roaming. A total of 1,301 (rural:585; urban:716) respondents (one per household) were interviewed of which 173 households (24.4%) in urban areas owned 237 dogs whilst 238 households (40.8%) in rural areas owned 353 dogs. The mean number of dogs per dog owning household was estimated to be 1.44 (urban:1.37 dogs; rural:1.48 dogs) and dogs per household was estimated to be 0.45 (urban:0.33; rural:0.60). The dog: human ratio was 1:16.30 (0.06 dogs per person) in urban areas and 1:8.43 (0.12 dogs per person) in rural areas. The total owned dog population based on the mean number of dogs per household and dogs per person were estimated to be 65,312 and 71,245 in the country, respectively. The male: female ratio of the owned dog was 1.31:1 in urban areas and 2.05:1 in rural areas. Majority of the dogs were local non-descript breeds in both urban (60.8%) and rural (78%) areas, and the most common source was acquisition from friends or family (44.7%). The stray dog population in Bhutan was estimated to be 48,379 (urban:22,772; rural:25,607). Of the total estimated owned dog population in the two border towns, the proportion that were found free-roaming was estimated to be 31%. The different dog population estimation methods were compared and discussed in this paper. This study generated baseline data on the demographic patterns of the owned and stray dogs in Bhutan which will be useful for planning and monitoring dog population management and rabies control program in the country.


Classified JPEG coding of mixed document images for printing.
This paper presents a modified JPEG coder that is applied to the compression of mixed documents (containing text, natural images, and graphics) for printing purposes. The modified JPEG coder proposed in this paper takes advantage of the distinct perceptually significant regions in these documents to achieve higher perceptual quality than the standard JPEG coder. The region-adaptivity is performed via classified thresholding being totally compliant with the baseline standard. A computationally efficient classification algorithm is presented, and the improved performance of the classified JPEG coder is verified.


Case-control meta-analysis of blood DNA methylation and autism spectrum disorder.
Several reports have suggested a role for epigenetic mechanisms in ASD etiology. Epigenome-wide association studies (EWAS) in autism spectrum disorder (ASD) may shed light on particular biological mechanisms. However, studies of ASD cases versus controls have been limited by post-mortem timing and severely small sample sizes. Reports from in-life sampling of blood or saliva have also been very limited in sample size and/or genomic coverage. We present the largest case-control EWAS for ASD to date, combining data from population-based case-control and case-sibling pair studies. DNA from 968 blood samples from children in the Study to Explore Early Development (SEED 1) was used to generate epigenome-wide array DNA methylation (DNAm) data at 485,512 CpG sites for 453 cases and 515 controls, using the Illumina 450K Beadchip. The Simons Simplex Collection (SSC) provided 450K array DNAm data on an additional 343 cases and their unaffected siblings. We performed EWAS meta-analysis across results from the two data sets, with adjustment for sex and surrogate variables that reflect major sources of biological variation and technical confounding such as cell type, batch, and ancestry. We compared top EWAS results to those from a previous brain-based analysis. We also tested for enrichment of ASD EWAS CpGs for being targets of meQTL associations using available SNP genotype data in the SEED sample. In this meta-analysis of blood-based DNA from 796 cases and 858 controls, no single CpG met a Bonferroni discovery threshold of p < 1.12 × 10- 7. Seven CpGs showed differences at p < 1 × 10- 5 and 48 at 1 × 10- 4. Of the top 7, 5 showed brain-based ASD associations as well, often with larger effect sizes, and the top 48 overall showed modest concordance (r = 0.31) in direction of effect with cerebellum samples. Finally, we observed suggestive evidence for enrichment of CpG sites controlled by SNPs (meQTL targets) among the EWAS CpG hits, which was consistent across EWAS and meQTL discovery p value thresholds. No single CpG site showed a large enough DNAm difference between cases and controls to achieve epigenome-wide significance in this sample size. However, our results suggest the potential to observe disease associations from blood-based samples. Among the seven sites achieving suggestive statistical significance, we observed consistent, and stronger, effects at the same sites among brain samples. Discovery-oriented EWAS for ASD using blood samples will likely need even larger samples and unified genetic data to further understand DNAm differences in ASD.


Intracellular Ca2+ thresholds that determine survival or death of energy-deprived cells.
Increase of intracellular ionized or free Ca2+ is thought to play a central role in cell death due to ATP depletion. However, concurrently operative mechanisms of injury that do not require intracellular Ca2+ increases have made it difficult to test this hypothesis or to determine the concentrations at which intracellular Ca2+ becomes lethal. The predominant Ca2+-independent mechanism of injury during ATP depletion involves the loss of cellular glycine. This type of damage can be fully inhibited by adding the amino acid exogenously. Using glycine to suppress Ca2+-independent plasma membrane damage, we have examined the effect of intracellular Ca2+ elevations on cell viability during ATP depletion. Madin-Darby canine kidney (MDCK) cells were depleted of ATP by incubation with a mitochondrial uncoupler in glucose-free medium. Free Ca2+ concentration in the medium was varied between 26 nmol/L and 1.25 mmol/L in the presence of a Ca2+ ionophore. Measurements with the Ca2+ probes fura-2, furaptra, and fura-2FF showed that intracellular Ca2+ was clamped at extracellular levels under these conditions. Cell survival during ATP depletion was indicated by viable cells recovered 24 hours later. The results show that ATP-depleted cells can sustain high levels of intracellular Ca2+ (100 micromol/L) for prolonged periods and remain viable if plasma membrane damage is prevented by glycine. Cell death was observed only when intracellular free Ca2+ was allowed to increase beyond 100 micromol/L, and this was associated with dramatic nuclear alterations: chromatin condensation, loss of nuclear lamins, and breakdown of DNA into large 50- to 150-kb fragments. Our studies demonstrate unexpectedly high resistance of cells to calcium cytotoxicity if glycine that is lost during ATP depletion is restored. In addition, they provide insights into novel mechanisms of nuclear disintegration and DNA damage that are triggered when the high thresholds of intracellular Ca2+ required for cell death are exceeded.


DNA extraction from crayfish exoskeleton.
Crayfish exoskeleton (CE) samples are generally less invasive and easy to be collected. However, it is difficult to extract DNA from them. This study was intended to investigate CE as a DNA source and design an easy and efficient DNA extraction protocol for polymerase chain reactions. Specific primer pair (PPO-F, PPO-R) was used to amplify extracted DNA from CE, and compared to crayfish tail muscle DNA sample. Moreover, seven microsatellites markers were used to amplify the CE DNA samples set. Since the extracted DNA from CE is suitable for gene amplification, the results present usefulness of CE as an easy and convenient DNA source for PCR-based population genetic research.


The role of CCK caerulein, and CCK antagonists in nociception.
The octapeptide form of CCK predominates in the central nervous system (CNS) of mammalian species, including man. Many of the physiological roles of CCK in the CNS are unknown, but it is believed to be involved in nociception. CCK is distributed throughout cortical grey matter, periaqueductal grey matter, ventromedial thalamus and spinal dorsal horn, all of which are areas known to be associated with pain modulation. CCK receptor subtypes have been identified and may be classified according to their affinity for the sulphated and desulphated forms of CCK-8 and the recently described selective antagonist. MK-329. CCK-A receptors have high affinity for sulphated CCK-8 and for MK-329 but low affinity for desulphated CCK-8 and CCK-4 whilst CCK-B sites bind MK-329 with low affinity and discriminate poorly between sulphated and desulphated CCK-8. CCK-A receptors are found predominantly in peripheral tissues but they also exist in discrete regions of the primate CNS, including the spinal cord. CCK-B receptors are found ubiquitously throughout other regions of the neuraxis. The results of studies on the effects of CCK-8 and the decapeptide analogue caerulein on pain thresholds are conflicting. Some workers suggest that large doses of CCK-8 and caerulein induce naloxone-reversible analgesia in certain pain models. However, it appears likely that analgesia induced by large doses of CCK and caerulein in animals may be a pharmacological rather than a physiological phenomenon. Accordingly, others have found that small (and most probably, physiological) doses of CCK-8 attenuate the analgesic effects of morphine, and of endogenous opioids. Thus, it has been proposed that CCK may act as an endogenous opiate antagonist. Studies in rats with the selective CCK antagonist MK-329 have helped clarify the interaction between CCK and morphine-induced analgesia. Treatment with MK-329 enhances morphine analgesia and chronic treatment with MK-329 prevents the development of tolerance to morphine analgesia. However, the antagonist does not prevent naloxone-precipitated withdrawal symptoms in morphine-dependent rats. In man, caerulein prevents pain associated with gall-bladder contraction, probably by relaxation of the sphincter of Oddi. Caerulein has also been shown to reduce renal colic and the pain of intermittent claudication. Preliminary clinical studies with the weak, non-selective, CCK antagonist proglumide, indicate an enhancement of morphine analgesia. As yet, no studies have demonstrated analgesic effects of CCK antagonists in man when administered alone.(ABSTRACT TRUNCATED AT 400 WORDS)


Depressive Symptom Clusters in Relation to Body Weight Status: Results From Two Large European Multicenter Studies.
Background: There is strong evidence for a bidirectional association between depression and obesity. Several biological, psychological, and behavior-related factors may influence this complex association. Clinical impression and preliminary evidence suggest that patients with a diagnosis of major depressive disorder may endorse very different depressive symptom patterns depending on their body weight status. Until now, little is known about potential differences in depressive symptoms in relation to body weight status. Objective: The aim of this analysis is the investigation of potential differences in depressive symptom clusters (mood symptoms, somatic/vegetative symptoms, and cognitive symptoms) in relation to body weight status. Methods: Cross-sectional baseline data were derived from two large European multicenter studies: the MooDFOOD Trial and the NESDA cohort study, including persons with overweight and obesity and normal weight reporting subthreshold depressive symptoms (assessment via Inventory of Depressive Symptomatology Self-Report, IDS-SR30). Different measures for body weight status [waist-to-hip ratio (WHR) and body mass index (BMI)] were examined. Propensity score matching was performed and multiple linear regression analyses were conducted. Results: A total of n = 504 individuals (73.0% women) were analyzed. Results show that more somatic/vegetative depressive symptoms, such as pain, change in appetite and weight, gastrointestinal symptoms, and arousal-related symptoms, were significantly associated with both a higher BMI and higher WHR, respectively. In addition, being male and older age were significantly associated with higher WHR. Mood and cognitive depressive symptoms did not yield significant associations for both body weight status measures. Conclusions: Somatic/vegetative symptoms and not mood and cognitive symptoms of depression are associated with body weight status. Thus, the results support previous findings of heterogeneous depressive symptoms in relation to body weight status. In addition to BMI, other body weight status measures for obesity should be taken into account in future studies. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02529423.


Farnesylation-defective Rheb Increases Axonal Length Independently of mTORC1 Activity in Embryonic Primary Neurons.
Rheb (Ras homolog enriched in the brain) is a small GTPase protein that plays an important role in cell signaling for development of the neocortex through modulation of mTORC1 (mammalian-target-of-rapamycin-complex-1) activity. mTORC1 is known to control various biological processes including axonal growth in forming complexes at the lysosomal membrane compartment. As such, anchoring of Rheb on the lysosomal membrane via the farnesylation of Rheb at its cysteine residue (C180) is required for its promotion of mTOR activity. To test the significance of Rheb farnesylation, we overexpressed a farnesylation mutant form of Rheb, Rheb C180S, in primary rat hippocampal neurons and also in mouse embryonic neurons using in utero electroporation. Interestingly, we found that Rheb C180S maintained promotional effect of axonal elongation similar to the wild-type Rheb in both test systems. On the other hand, Rheb C180S failed to exhibit the multiple axon-promoting effect which is found in wild-type Rheb. The levels of phospho-4EBP1, a downstream target of mTORC1, were surprisingly increased in Rheb C180S transfected neurons, despite the levels of phosphorylated mTOR being significantly decreased compared to control vector transfectants. A specific mTORC1 inhibitor, rapamycin, also could not completely abolish axon elongation characteristics of Rheb C180S in transfected cells. Our data suggests that Rheb in a non-membrane compartment can promote the axonal elongation via phosphorylation of 4EBP1 and through an mTORC1-independent pathway.


Single cell swimming dynamics of Listeria monocytogenes using a nanoporous microfluidic platform.
Listeria monocytogenes remains a significant foodborne pathogen due to its virulence and ability to become established in food processing facilities. The pathogen is characterized by its ability to grow over a wide temperature range and withstand a broad range of stresses. The following reports on the chemotaxis and motility of the L. monocytogenes when exposed to relatively small concentrations of acetic acid. Using the developed nanoporous microfluidic device to precisely modulate the cellular environment, we exposed the individual Listeria cells to acetic acid and, in real time and with high resolution, observed how the cells reacted to the change in their surroundings. Our results showed that concentrations of acetic acid below 10 mM had very little, if any, effect on the motility. However, when exposed to 100 mM acetic acid, the cells exhibited a sharp drop in velocity and displayed a more random pattern of motion. These results indicate that at appropriate concentrations, acetic acid has the ability to disable the flagellum of the cells, thus impairing their motility. This drop in motility has numerous effects on the cell; its main effects being the obstruction of the cell's ability to properly form biofilms and a reduction in the overall infectivity of the cells. Since these characteristics are especially useful in controlling the proliferation of L. monocytogenes, acetic acid shows potential for application in the food industry as an active compound in designing a food packaging environment and as an antimicrobial agent.


Informal support to first-parents after childbirth: a qualitative study in low-income suburbs of Dar es Salaam, Tanzania.
In Tanzania, and many sub-Saharan African countries, postpartum health programs have received less attention compared to other maternity care programs and therefore new parents rely on informal support. Knowledge on how informal support is understood by its stakeholders to be able to improve the health in families after childbirth is required. This study aimed to explore discourses on health related informal support to first-time parents after childbirth in low-income suburbs of Dar es Salaam, Tanzania. Thirteen focus group discussions with first-time parents and female and male informal supporters were analysed by discourse analysis. The dominant discourse was that after childbirth a first time mother needed and should be provided with support for care of the infant, herself and the household work by the maternal or paternal mother or other close and extended family members. In their absence, neighbours and friends were described as reconstructing informal support. Informal support was provided conditionally, where poor socio-economic status and non-adherence to social norms risked poor support. Support to new fathers was constructed as less prominent, provided mainly by older men and focused on economy and sexual matters. The discourse conveyed stereotypic gender roles with women described as family caretakers and men as final decision-makers and financial providers. The informal supporters regulated the first-time parents' contacts with other sources of support. Strong and authoritative informal support networks appear to persist. However, poverty and non-adherence to social norms was understood as resulting in less support. Family health in this context would be improved by capitalising on existing informal support networks while discouraging norms promoting harmful practices and attending to the poorest. Upholding stereotypic notions of femininity and masculinity implies great burden of care for the women and delimited male involvement. Men's involvement in reproductive and child health programmes has the potential for improving family health after childbirth. The discourses conveyed contradicting messages that may be a source of worry and confusion for the new parents. Recognition, respect and raising awareness for different social actors' competencies and limitations can potentially create a health-promoting environment among families after childbirth.


Financial burden of medical out-of-pocket spending by state and the implications of the 2014 Medicaid expansions.
This study is the first to offer a detailed look at the burden of medical out-of-pocket spending, defined as total family medical out-of-pocket spending as a proportion of income, for each state. It further investigates which states have greater shares of individuals with high burden levels and no Medicaid coverage but would be Medicaid eligible under the 2014 rules of the Affordable Care Act should their state choose to participate in the expansion. This work suggests which states have the largest populations likely to benefit, in terms of lowering medical spending burden, from participating in the 2014 adult Medicaid expansions.


Presentation of HIV V3 loop epitopes for enhanced antigenicity, immunogenicity and diagnostic potential.
To evaluate the immunological properties of a panel of human mucin MUC1/HIV V3 loop chimeras. The immunodominant epitope of MUC1 (APDTR) was found to be structurally isomorphous with the tip of the principle neutralizing determinant (PND) of HIV-1 (MN) (GPGRA). A panel of 120 residue, six tandem repeat (TR) and 60 residue, three TR chimeric antigens were constructed in which the repeating MUC1 epitope is replaced by HIV-1 PND. Each 20 residue TR contains one PND epitope. The PND of HIV-1 is presented in the native beta-turn conformation at the crest of each repeating knob structure of the mucin-like protein. The antigenicity of the chimeric antigens were compared using enzyme-linked immunosorbent assay (ELISA) and HIV-infected patient sera. Structural effects of antibody-antigen interactions were determined using surface plasmon resonance, with human monoclonal antibodies, chimeric antigens and the cyclic and linear V3 loops. Immunogenicity of three versus six TR was measured in mice. Nine residues of the HIV PND substituted into the mucin backbone were equivalent to the 36 residue cyclic V3 loop in ELISA. The 120 residue antigens induced high titer, immunoglobulin (Ig) M and IgG, and HIV-specific antibodies in mice. MUC1/V3 chimeras efficiently detect HIV-specific antibodies in patient sera. Multivalent presentation of the PND is advantageous for higher affinity antibody-antigen interactions and for inducing HIV-specific IgM and IgG antibodies.


Ultrasound and magnetic resonance imaging findings in Schistosomiasis mansoni: expanded gallbladder fossa and fatty hilum signs.
There is no study relating magnetic resonance imaging (MRI) to ultrasound (US) findings in patients with Schistosomiasis mansoni. Our aim was to describe MRI findings inpatients with schistosomal liver disease identified by US. Fifty-four patients (mean age 41.6±13.5years) from an area endemic for Schistosomiasis mansoni were selected for this study.All had US indicating liver schistosomal fibrosis and were evaluated with MRI performed witha 1.5-T superconducting magnet unit (Sigma). Forty-seven (87%) of the 54 patientsshowing signs of periportal fibrosis identified through US investigation had confirmed diagnosesby MRI. In the seven discordant cases (13%), MRI revealed fat tissue filling in the hilar periportalspace where US indicated isolated thickening around the main portal vein at its point of entryto the liver. We named this the fatty hilum sign. One of the 47 patients with MRI evidence ofperiportal fibrosis had had his gallbladder removed previously. Thirty-five (76.1%) of the other46 patients had an expanded gallbladder fossa filled with fat tissue, whereas MRI of the remainingeleven showed pericholecystic signs of fibrosis. Echogenic thickening of thegallbladder wall and of the main portal vein wall heretofore attributed to fibrosis were frequentlyidentified as fat tissue in MRI. However, the gallbladder wall thickening shown in US (expandedgallbladder fossa in MRI) is probably secondary to combined hepatic morphologic changes inschistosomiasis, representing severe liver involvement.


Screening of potential anti-adipogenic effects of phenolic compounds showing different chemical structure in 3T3-L1 preadipocytes.
This study was designed to analyze the anti-adipogenic effect of fifteen phenolic compounds from various chemical groups in 3T3-L1 pre-adipocytes. Cells were treated with 25 μM, 10 μM or 1 μM of apigenin, luteolin, catechin, epicatechin, epigallocatechin, genistein, daizein, naringenin, hesperidin, quercetin, kaempferol, resveratrol, vanillic acid, piceatannol and pterostilbene for 8 days. At 25 μM lipid accumulation was reduced by all the compounds, with the exception of catechin, epicatechin and epigallocatechin. At a dose of 10 μM apigenin, luteolin, naringenin, hesperidin, quercetin and kaempferol induced significant reductions, and at 1 μM only naringenin, hesperidin and quercetin were effective. The expression of c/ebpα was not. C/ebpβ was significantly reduced by genistein and kaempferol, pparγ by genistein and pterostilbene, srebp1c by luteolin, genistein, hesperidin, kaempferol, pterostilbene and vanillic acid, and lpl by kaempferol. In conclusion, the most effective phenolic compounds are naringenin, hesperidin and quercetin. Differences were found in terms of effects on the expression of genes involved in adipogenesis among the analyzed compounds.


Effects of exercise on tenocyte cellularity and tenocyte nuclear morphology in immature and mature equine digital tendons.
The injury-prone, energy-storing equine superficial digital flexor tendon (SDFT) of the mature performance horse has a limited ability to respond to exercise in contrast with the noninjury-prone, anatomically opposing common digital extensor tendon (CDET). Previous studies have indicated low levels of cellular activity in the mature SDFT, but in foal tendons the tenocytes may still have the ability to adapt positively to increased exercise. To measure tenocyte densities and types in histological sections from the SDFT and CDET of horses from controlled long-term, short-term and foal exercise studies. Specimens were collected from mid-metacarpal segments of the CDET and SDFT for each horse and processed for histology; central and peripheral regions of the SDFT cross-section were analysed separately (SDFTc, SDFTp). Tenocyte nuclei were counted in a total area of 1.59 mm(2) for each tendon region in each horse. Each nucleus was classified as type 1 (elongate and thin), type 2 (ovoid and plump) or type 3 (chondrocyte-like); type 1 cells are proposed to be less synthetically active than type 2 cells. No significant differences were noted between exercise and control groups in any of the studies, with the exception of an exercise-related reduction in the proportion of type 1 tenocytes for all tendons combined in the long-term study. There were tendon- and site-specific differences in tenocyte densities and proportions of type 1 and 2 cells in all 3 studies. There was no indication that exercise increased tenocyte density or proportions of the (theoretically) more active type 2 cells in immature horses (short-term and foal studies), perhaps because the training regimens did not achieve certain threshold strain levels. In the foal study these findings can still be interpreted positively as evidence that the training regimen did not induce subclinical damage.


Efficacy and safety of curcumin in primary sclerosing cholangitis: an open label pilot study.
Goals: To assess if curcumin improves markers of cholestasis among subjects with primary sclerosing cholangitis (PSC). Background: PSC is a chronic cholestatic liver disorder for which there is no established medical therapy. Preclinical data suggest curcumin may have a beneficial effect in PSC. Study: Subjects with PSC and a serum alkaline phosphatase (SAP) greater than 1.5 times the upper limit of normal (ULN) received curcumin 750 mg orally twice daily for 12 weeks in an open-label pilot study. The primary composite endpoint was proportion of subjects who had a reduction of SAP to less than 1.5 times ULN or a 40% reduction in SAP between baseline and week 12. Secondary endpoints included changes in serum aspartate aminotransferase, total bilirubin, Mayo PSC risk score and self-reported health questionnaires. Results: Two-hundred and fifty-eight patients with PSC were screened and 15 subjects were enrolled and all completed 12 weeks of therapy. The most common reason for subject exclusion was SAP less than 1.5 times the ULN (n = 98). Curcumin did not result in a significant median (interquartile range) change in SAP times the ULN [3.43 (2.10-4.32) to 2.46 (1.89-4.41), p = .36], and only 20% (3/15) subjects achieved the primary endpoint. Similarly, there was no significant change in the secondary endpoints. There were no serious adverse events reported. Conclusion: While curcumin was well tolerated, it was not associated with significant improvements in cholestasis or symptoms. Moreover, this study also illustrates that a low SAP is common among those with PSC. Abbreviations PSC: Primary sclerosing cholangitis; IBD: inflammatory bowel disease; CCA: cholangiocarcinoma; SAP: serum alkaline phosphatase; ULN: upper limit of normal; UDCA: ursodeoxycholic acid; CRP: c-reactive protein; AST: aspartate aminotransferase; ALT: alanine aminotransferase; INR: international normalized ratio; FIS: fatigue impact scale; AE: adverse events; PREsTo: PSC risk estimate tool; IQR: interquartile range; ELF: enhanced liver fibrosis.


Changes in Aspergillus nidulans gene expression induced by bafilomycin, a Streptomyces-produced antibiotic.
In natural environments bacteria and filamentous fungi often compete for the same resources. Consequently, production of antibiotic secondary metabolites and defence mechanisms against these compounds have evolved in these organisms. An experimental model has been developed to study the response in fungi exposed to one such antibiotic. The filamentous fungus Aspergillus nidulans was treated with bafilomycin B1, a Streptomyces-produced antibiotic which reduces radial growth rate and induces morphological changes in fungi. mRNA differential display was used to study changes in fungal gene expression. For five genes, changes in abundance of the corresponding mRNAs, directly or indirectly caused by bafilomycin, were observed. Of these, three were up-regulated and two repressed. With four of these the change in mRNA abundance measured ranged from 10- to 60-fold. However, for one gene the mRNA was only detected after bafilomycin treatment. One of the down-regulated mRNAs encodes ASPND1, a glycoprotein that belongs to a known family of antigens identified in aspergilloma patients. One up-regulated mRNA shows sequence similarities, at the amino acid level, with a cell-wall protein of Saccharomyces cerevisiae. The remaining three genes were also cloned and sequenced; their sequences do not correspond to known genes in A. nidulans, and no similarities with published nucleotide or protein sequences in other organisms were found. These results indicate the feasibility of using mRNA differential display to study interactions between bacteria and filamentous fungi.


Correlation between CSF and blood neurofilament light chain protein: a systematic review and meta-analysis.
To assess the overall pooled correlation coefficient estimate between cerebrospinal fluid (CSF) and blood neurofilament light (NfL) protein. We searched Medline, Embase and Web of Science for published articles, from their inception to 9 July 2019, according to Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Studies reporting the correlation between CSF and blood NfL in humans were included. We conducted a random-effects meta-analysis to calculate the overall pooled correlation coefficient estimate, accounting for correlation technique and assay used. Heterogeneity was assessed using the I2 statistic test. In sensitivity analyses, we calculated the pooled correlation coefficient estimate according to blood NfL assay: single-molecule array digital immunoassay (Simoa), electrochemiluminescence (ECL) assay or ELISA. Data were extracted from 36 articles, including 3961 paired CSF and blood NfL samples. Overall, 26/36 studies measured blood NfL using Simoa, 8/36 ECL, 1/36 ELISA and 1 study reported all three assay results. The overall meta-analysis demonstrated that the pooled correlation coefficient estimate for CSF and blood NfL was r=0.72. Heterogeneity was significant: I2=83%, p<0.01. In sensitivity analyses, the pooled correlation coefficient was similar for studies measuring blood NfL using Simoa and ECL (r=0.69 and r=0.68, respectively) but weaker for ELISA (r=0.35). Moderate correlations are demonstrated between CSF and blood NfL, especially when blood NfL was measured using Simoa and ECL. Given its high analytical sensitivity, Simoa is the preferred assay for measuring NfL, especially at low or physiological concentrations, and this meta-analysis supports its use as the current most advanced surrogate measure of CSF NfL. CRD42019140469.


Dietary fatty acids regulate acyl-CoA:cholesterol acyltransferase and cytosolic cholesteryl ester hydrolase in hamsters.
To investigate the effects of dietary fatty acids on acyl-CoA:cholesterol acyltransferase (ACAT) and cytosolic cholesteryl ester hydrolase (cCEH), male Syrian hamsters (F(1)B hybrid) were fed a modified version of the NIH-07 open formula, cereal-based rodent diet enriched with one of the following 4 dietary fatty acids: palmitic acid (16:0), trans fatty acids (18:1t), oleic acid (18:1c), or linoleic acid (18:2). Hamsters fed 16:0 and 18:1t had significantly higher plasma non-HDL cholesterol concentrations compared with those fed 18:1c and 18:2. However, differences in plasma apolipoprotein (apo)B(100) concentration, hepatic cCEH mRNA abundance, and hepatic ACAT activity between 16:0- and 18:1t-fed hamsters suggest that the hypercholesterolemic effects are achieved by different mechanisms. Specifically, an increase in ACAT activity by 16:0 may induce enrichment of cholesteryl esters in apoB(100)-containing particles, whereas 18:1t may increase the number of the particles. Hepatic cholesteryl esters accumulated in the 18:1c- and 18:2-fed groups with no differences in hepatic ACAT activity and cCEH mRNA abundance among hamsters fed unsaturated fatty acids (i.e., 18:1t, 18:1c, and 18:2). Considering the lack of change in free cholesterol concentration and increased cholesteryl esters in the liver, the hypocholesterolemic effect of 18:1c and 18:2 compared with 18:1t may be attributed to decreased production of apoB(100)-containing particles. ACAT-1 was expressed in all the tissues examined; in contrast, ACAT-2 was highly expressed in the liver and small intestine. Hepatic ACAT activity was disproportionate to the levels of ACAT-1 and ACAT-2 mRNA and protein, indicating post-transcriptional regulation of ACAT by dietary fatty acids. The data suggest that cholesterolemic effects of individual dietary fatty acids can be achieved through their independent modulation of pathways regulating assembly and secretion of apoB(100)-containing particles.


Imagining the impossible before breakfast: the relation between creativity, dissociation, and sleep.
Dissociative symptoms have been related to higher rapid eye movement sleep density, a sleep phase during which hyperassociativity may occur. This may enhance artistic creativity during the day. To test this hypothesis, we conducted a creative photo contest to explore the relation between dissociation, sleep, and creativity. During the contest, participants (N = 72) took one photo per day for five consecutive days, based on specific daily themes (consisting of single words) and the instruction to take as creative a photo as possible each day. Furthermore, they completed daily measures of state dissociation and a short sleep diary. The photos and their captions were ranked by two professional photographers and two clinical psychologists based on creativity, originality, bizarreness, and quality. We expected that dissociative people would rank higher in the contest compared with low-dissociative participants, and that the most original photos would be taken on days when the participants scored highest on acute dissociation. We found that acute dissociation predicted a higher ranking on creativity. Poorer sleep quality and fewer hours of sleep predicted more bizarreness in the photos and captions. None of the trait measures could predict creativity. In sum, acute dissociation related to enhanced creativity. These findings contribute to our understanding of dissociative symptomatology.


Comparative electrochemical and photophysical studies of tetrathiafulvalene-annulated porphyrins and their Zn(II) complexes: the effect of metalation and structural variation.
A series of tetrathiafulvalene (TTF)-annulated porphyrins, and their corresponding Zn(II) complexes, have been synthesized. Detailed electrochemical, photophysical, and theoretical studies reveal the effects of intramolecular charge-transfer transitions that originate from the TTF fragments to the macrocyclic core. The incremental synthetic addition of TTF moieties to the porphyrin core makes the species more susceptible to these charge-transfer (CT) effects as evidenced by spectroscopic studies. On the other hand, regular positive shifts in the reduction signals are seen in the square-wave voltammograms as the number of TTF subunits increases. Structural studies that involve the tetrakis-substituted TTF-porphyrin (both free-base and Zn(II) complex) reveal only modest deviations from planarity. The effect of TTF substitution is thus ascribed to electronic overlap between annulated TTF subunits rather than steric effects. The directly linked thiafulvalene subunits function as both π acceptors as well as σ donors. Whereas σ donation accounts for the substituent-dependent charge-transfer transitions, it is the π-acceptor nature of the appended tetrathiafulvalene groups that dominates the redox chemistry. Interactions between the subunits are also reflected in the square-wave voltammograms. In the case of the free-base derivatives that bear multiple TTF subunits, the neighboring TTF units, as well as the TTF(⋅+) generated through one-electron oxidation, can interact with each other; this gives rise to multiple signals in the square-wave voltammograms. On the other hand, after metalation, the electronic communication between the separate TTF moieties becomes restricted and they act as separate redox centers under conditions of oxidation. Thus only two signals, which correspond to TTF(⋅+) and TTF(2+), are observed. The reduction potentials are also seen to shift towards more negative values after metalation, a finding that is considered to reflect an increased HOMO-LUMO gap. To probe the excited-state dynamics and internal CT character, transient absorption spectral studies were performed. These analyses revealed that all the TTF-porphyrins of this study display relatively short excited-state lifetimes, which range from 1 to 20 ps. This reflects a very fast decay to the ground state and is consistent with the proposed intramolecular charge-transfer effects inferred from the ground-state studies. Complementary DFT calculations provide a mechanistic rationale for the electron flow within the TTF-porphyrins and support the proposed intramolecular charge-transfer interactions and π-acceptor effects.


First Report of Verticillium Wilt Caused by V. dahliae on Grafted Solanum aethiopicum in Washington.
Solanum aethiopicum L., previously S. integrifolium Poir. (4), has been used as a rootstock for commercial, grafted eggplant production throughout Asia (3). In August 2010 and 2011, symptoms of Verticillium wilt were observed on 'Epic' eggplant (S. melongena L.) grafted onto S. aethiopicum at two sites with a history of the disease: one in the irrigated, dryland Columbia Basin of eastern Washington near Eltopia, and the other in maritime western Washington near Mount Vernon. Interveinal chlorosis, V-shaped necrotic lesions, and wilting were evident at both sites in both years. Each year, stems of 20 symptomatic plants from each field site were cut at the soil line to a 20-cm length, surface sterilized for 5 min in a 10% bleach solution, rinsed in tap water for 30 s, cut longitudinally, and incubated in moisture chambers for 4 weeks at room temperature in the dark. Microsclerotia that formed in the stems were typical of those produced by V. dahliae. One isolate, 'MVEgg301', from an infected stem at Mount Vernon, developed dark microsclerotia and verticillate conidiophores in a radiating pattern, typical of Verticillium on half-strength potato dextrose agar (1/2 PDA) medium. The internal transcribed spacer (ITS) region of rDNA amplified by PCR assay using primers ITS6 and ITS4 from mycelia sampled directly from 1/2 PDA media revealed a 100% match with ITS rDNA sequences of >50 V. dahliae accessions in GenBank (1). Pathogenicity of 'MVEgg301' was assessed in two tests. In both, 12 each of non-grafted and grafted (with cv. Epic) S. aethiopicum plants were inoculated with 'MVEgg301' by cutting approximately 5 mm off the root tips and dipping the remaining roots in a suspension of 106 conidia/ml for 5 s. Similarly, 12 each of non-grafted and grafted S. aethiopicum plants were cut and dipped similarly in sterile water as controls. Chlorosis, necrosis, and wilting were observed in 11 of the 12 inoculated, non-grafted plants and 8 of the 12 inoculated, grafted plants in Test I. The same symptoms were observed in 10 of the 12 inoculated, non-grafted plants and 10 of the 12 inoculated, grafted plants in Test II. V. dahliae was reisolated and confirmed from symptomatic, inoculated non-grafted and grafted plants using the stem assay and direct PCR assay described above. Chlorosis, necrosis, and wilting were observed in one non-grafted control plant in Test I, and two non-grafted and four grafted control plants in Test II. The symptoms were mild and likely due to nutritional deficiencies; microsclerotia were not observed in any assayed water-inoculated plant stems. Although there are several reports of V. albo-atrum infecting S. aethiopicum in the United States (2), to our knowledge, this is the first report of V. dahliae causing Verticillium wilt on this eggplant species. This finding is significant because S. aethiopicum is used as a rootstock for control of soilborne diseases like Verticillium wilt in commercial grafted eggplant production (3). References: (1) G. Calmin et al. Biotechnol. Biotechnol. Equ. 21:40, 2007. (2) D. F. Farr et al. Fungi on Plants and Plant Products in the United States. American Phytopathological Society, St. Paul, MN, 1989. (3) M. Oda. Food Fert. Technol. Ctr. Ext. Bul. 480:1, 1999. (4) PBI Solanum Project. 2012. Solanaceae Source. Accessed at http://www.nhm.ac.uk/solanaceaesource/ . Natural History Museum, London, 29 Aug. 2012.


Selective interactions of polyanions with basic surfaces on human immunodeficiency virus type 1 gp120.
It is well established that the gp120 V3 loop of T-cell-line-adapted human immunodeficiency virus type 1 (HIV-1) binds both cell-associated and soluble polyanions. Virus infectivity is increased by interactions between HIV-1 and heparan sulfate proteoglycans on some cell types, and soluble polyanions such as heparin and dextran sulfate neutralize HIV-1 in vitro. However, the analysis of gp120-polyanion interactions has been limited to T-cell-line-adapted, CXCR4-using virus and virus-derived gp120, and the polyanion binding ability of gp120 regions other than the V3 loop has not been addressed. Here we demonstrate by monoclonal-antibody inhibition, labeled heparin binding, and surface plasmon resonance studies that a second site, most probably corresponding to the newly defined, highly conserved coreceptor binding region on gp120, forms part of the polyanion binding surface. Consistent with the binding of polyanions to the coreceptor binding surface, dextran sulfate interfered with the gp120-CXCR4 association while having no detectable effect on the gp120-CD4 interaction. The interaction between polyanions and X4 or R5X4 gp120 was readily detectable, whereas weak or undetectable binding was observed with R5 gp120. Analysis of mutated forms of X4 gp120 demonstrated that the V3 loop is the major determinant for polyanion binding whereas other regions, including the V1/V2 loop structure and the NH(2) and COOH termini, exert a more subtle influence. A molecular model of the electrostatic potential of the conserved coreceptor binding region confirmed that it is basic but that the overall charge on this surface is dominated by the V3 loop. These results demonstrate a selective interaction of gp120 with polyanions and suggest that the conserved coreceptor binding surface may present a novel and conserved target for therapeutic intervention.


Interactions of Multiple Spin-2 Fields beyond Pairwise Couplings.
Thus far, all known ghost-free interactions of multiple spin-2 fields have involved at most pairwise couplings of the fields, which are direct generalizations of bimetric interactions. We present a class of spin-2 theories with genuine multifield interactions and explicitly demonstrate the absence of ghost instabilities. The construction involves integrating out a nondynamical field in a theory of spin-2 fields with only pairwise ghost-free interactions. The new multivierbein interactions generated are not always expressible in terms of the associated metrics.


EPSPs in rat neocortical neurons in vitro. I. Electrophysiological evidence for two distinct EPSPs.
1. To investigate excitatory postsynaptic potentials (EPSPs), intracellular recordings were performed in layer II/III neurons of the rat medial frontal cortex. The average resting membrane potential of the neurons was more than -75 mV and their average input resistance was greater than 20 M omega. The amplitudes of the action potentials evoked by injection of depolarizing current pulses were greater than 100 mV. The electrophysiological properties of the neurons recorded were similar to those of regular-spiking pyramidal cells. 2. Current-voltage relationships, determined by injecting inward and outward current pulses, displayed considerable inward rectification in both the depolarizing and hyperpolarizing directions. The steady-state input resistance increased with depolarization and decreased with hyperpolarization, concomitant with increases and decreases, respectively, in the membrane time constant. 3. Postsynaptic potentials were evoked by electrical stimulation via a bipolar electrode positioned in layer IV of the neocortex. Stimulus-response relationships, determined by gradually increasing the stimulus intensity, were consistent among the population of neurons examined. A short-latency EPSP [early EPSP (eEPSP)] was the response with the lowest threshold. Amplitudes of the eEPSP ranged from 4 to 8 mV. Following a hyperpolarization of the membrane potential, the amplitude of the eEPSP decreased. Upon depolarization, a slight increase in amplitude and duration was observed, accompanied by a significant increase in time to peak. 4. The membrane current underlying the eEPSP (eEPSC) was measured using the single-electrode voltage-clamp method. The amplitude of the eEPSC was apparently independent of the membrane potential in 8 of 12 neurons tested. In the other 4 neurons, the amplitude of the eEPSC increased with hyperpolarization and decreased with depolarization. 5. Higher stimulus intensities evoked, in addition to the eEPSP, a delayed EPSP [late EPSP (lEPSP)] in greater than 90% of the neurons tested. The amplitude of the lEPSP ranged from 12 to 20 mV, and the latency varied between 20 and 60 ms. The amplitude of the lEPSP varied with membrane potential, decreasing with depolarization and increasing following hyperpolarization. The membrane current underlying the lEPSP (lEPSC) displayed a similar voltage dependence. 6. At stimulus intensities that led to the activation of inhibitory postsynaptic potentials (IPSPs), the lEPSP was no longer observed.(ABSTRACT TRUNCATED AT 400 WORDS)


A triplication of the Williams-Beuren syndrome region in a patient with mental retardation, a severe expressive language delay, behavioural problems and dysmorphisms.
Intrachromosomal triplications are rare chromosomal rearrangements. In most triplication cases the phenotype is similar to, but more severe than observed in patients with a duplication of the same region. The Williams-Beuren syndrome (WBS) region on 7q11.23, is prone to chromosomal rearrangements. A common deletion causes the well-characterised Williams-Beuren syndrome. The reciprocal duplication has been described in 27 families only, and is associated with a variable phenotype, including speech delay with (mild) mental retardation, autism and mild dysmorphic features. As the duplication of the WBS region is sometimes found inunaffected parents, initially some doubts have been raised about the pathogenicity of the duplication. We here describe the first triplication of a large part of the WBS region, detected with array CGH and confirmed by MLPA and FISH. The phenotypic features include mental retardation, a severe expressive language delay, behavioural problems and dysmorphisms. These features are remarkably similar, but seem more severe, compared to features seen in duplication patients. Therefore, our findings support the idea that an amplification of the WBS region is a disease-causing event, although the penetrance might be incomplete.


Measurement of global functional performance in patients with rheumatoid arthritis using rheumatology function tests.
Outcome assessment in patients with rheumatoid arthritis (RA) includes measurement of physical function. We derived a scale to quantify global physical function in RA, using three performance-based rheumatology function tests (RFTs). We measured grip strength, walking velocity, and shirt button speed in consecutive RA patients attending scheduled appointments at six rheumatology clinics, repeating these measurements after a median interval of 1 year. We extracted the underlying latent variable using principal component factor analysis. We used the Bayesian information criterion to assess the global physical function scale's cross-sectional fit to criterion standards. The criteria were joint tenderness, swelling, and deformity, pain, physical disability, current work status, and vital status at 6 years after study enrolment. We computed Guyatt's responsiveness statistic for improvement according to the American College of Rheumatology (ACR) definition. Baseline functional performance data were available for 777 patients, and follow-up data were available for 681. Mean +/- standard deviation for each RFT at baseline were: grip strength, 14 +/- 10 kg; walking velocity, 194 +/- 82 ft/min; and shirt button speed, 7.1 +/- 3.8 buttons/min. Grip strength and walking velocity departed significantly from normality. The three RFTs loaded strongly on a single factor that explained >or=70% of their combined variance. We rescaled the factor to vary from 0 to 100. Its mean +/- standard deviation was 41 +/- 20, with a normal distribution. The new global scale had a stronger fit than the primary RFT to most of the criterion standards. It correlated more strongly with physical disability at follow-up and was more responsive to improvement defined according to the ACR20 and ACR50 definitions. We conclude that a performance-based physical function scale extracted from three RFTs has acceptable distributional and measurement properties and is responsive to clinically meaningful change. It provides a parsimonious scale to measure global physical function in RA.


Clinical significance of clonality and Epstein-Barr virus infection in adult patients with hemophagocytic lymphohistiocytosis.
We assessed the clinical significance of T or B cell clonality and Epstein-Barr virus (EBV) infection in adult patients with hemophagocytic lymphohistiocytosis (HLH) to identify factors related to prognosis. A total of 30 adult patients with diagnosed HLH were included in the study. In all patients, EBV-DNA in peripheral blood was examined by quantitative real-time polymerase chain reaction and bone marrow cells were examined for clonal rearrangement of T cell receptor gamma(TCRG) and immunoglobulin heavy chain (IGH) genes. TCRG clones were detected in 10 patients (33.3%) and IGH clones were detected in 8 patients (26.7%). We found no correlation between clonality and patient outcome. The patients less than 1,000 copies (mL)21 of EBVDNA showed a significantly higher clinical response (P 5 0.008) and longer overall survival (P 5 0.01) than those with high viral load of EBV-DNA. Our results suggest that TCRG and IGH rearrangement do not have any clinical significance in adult patients with HLH, but that high viral load of EBV-DNA may be a risk factor for poor outcomes. In HLH, high viral load of EBV-DNA should thus suggest a prompt approach with aggressive therapeutic interventions.


The role of molecular analysis in cutaneous lymphomas.
The purpose of this review is to summarize the most important molecular techniques for the diagnosis of cutaneous lymphomas. When making a diagnosis, we are looking for the solid clinicopathological correlation. Molecular analysis includes immunophenotyping and clonality analysis, and is important for 2 principal reasons: (1) to confirm the diagnosis in cases where the clinical and/or pathological presentations are nondiagnostic, and (2) to further characterize the nature of the lymphoma. More specifically, we are trying to discern whether the lymphoma is primarily cutaneous or systemic with secondary skin involvement, and we are also attempting to subclassify the tumor. Recently, many techniques have provided a more accurate diagnosis of cutaneous lymphomas and some prognostic implications, including polymerase chain reaction, fluorescence in situ hybridization, and flow cytometry. Fluorescence in situ hybridization is not routinely used in the diagnosis of cutaneous lymphoma, but many studies have shown potential future applications in various areas. Other techniques, such as comparative genomic hybridization, are still confined to the research arena, but have added some insight into the molecular pathogenesis of cutaneous T-cell lymphoma.


High precision optical characterization of semiconductor saturable absorber mirrors.
Semiconductor saturable absorber mirrors (SESAMs) have become a key element of many ultrafast laser sources, enabling passively modelocked lasers with >100 GHz repetition rate or with >10 microJ pulse energy. Precise knowledge of the nonlinear optical reflectivity is required to optimize the SESAMs for self-starting passive modelocking at record high repetition rates or pulse energies. In this article, we discuss a new method for wide dynamic range nonlinear reflectivity measurements. We achieve a higher accuracy (<0.05%) with a simpler and more cost-efficient measurement scheme compared with previous measurement systems. The method can easily be implemented for arbitrary wavelength regions and fluence ranges.


Occlusal schemes for complete dentures: a systematic review.
The aim of this study was to qualitatively review the literature regarding occlusal schemes for complete dentures. An electronic search was executed using PubMed (MEDLINE) with the aid of Boolean operators to combine the following terms: "complete denture," "occlusion," "balanced," "lingualized," "anatomic," "flat," "monoplane," and "canine." The search was limited to English peer-reviewed articles published up to January 2012. The literature search was supplemented by manual searching of relevant journals and the reference lists of selected articles. A total of 565 articles were retrieved; however, only 12 articles met the inclusion criteria. The included studies evaluated the effects of posterior tooth morphology/arrangement and lateral occlusal guidance. In relation to morphology, the posterior teeth were either anatomical or flat. The posterior tooth arrangements showed conventional bilaterally balanced occlusion (CBBO), lingualized bilaterally balanced occlusion (LBBO), or monoplane occlusion (MO). The lateral occlusal guidance involved either balanced occlusion or anterior tooth-guided occlusion (ATGO). Within the limitations of this review, it can be concluded that anatomical teeth arranged in CBBO or LBBO are preferable to flat teeth arranged in MO. This is primarily related to patient acceptance. ATGO can also be considered for complete dentures.


Luteinizing hormone response of castrated rabbits to treatment with testosterone propionate and estradiol benzoate.
The effects of sex steroids on luteinizing hormone (LH) secretion in rabbits of both sexes castrated for at least 2 weeks previously were investigated. An intramuscular (i.m.) injection of testosterone propionate (TP) or estradiol benzoate (EB) was given about midway through blood sampling which ranged from 6 to 12 h. LH and steroids were measured by established radioimmunoassay (RIA) procedures. Variable responses were obtained with animals. Castration itself in most instances led to increases in circulating levels of LH which ranged from normal levels to greater than 200 ng/ml with some evidence for episodic variation. EB was more effective than TP in reducing LH levels and inhibiting episodic release.


A new type D retrovirus isolated from macaques with an immunodeficiency syndrome.
Macaque monkeys with the recently described acquired immunodeficiency syndrome show a marked defect in T-lymphocyte function and die with opportunistic infections and lymphoproliferative abnormalities. In the study described here a new type D retrovirus was isolated from two Macaca cyclopis with this syndrome. This virus is related to, but distinct from, Mason-Pfizer monkey virus, a type D retrovirus previously isolated from a mammary tumor of a rhesus monkey (Macaca mulatta).


Pertrochanteric Calcifications in Patients With Greater Trochanteric Pain Syndrome: Description, Prevalence, and Correlation With Intraoperatively Diagnosed Hip Abductor Tendon Injuries.
Pertrochanteric calcifications can be found in patients with greater trochanteric pain syndrome (GTPS). A systematic description of the types and prevalence of these calcifications has not been undertaken. Furthermore, there is conflicting evidence regarding their association with abductor tendon injuries. (1) To describe the various types and prevalence of pertrochanteric calcifications in patients presenting for the surgical management of recalcitrant GTPS. (2) To evaluate the association of the various calcifications with intraoperatively diagnosed hip abductor tendon injuries, including tendinosis, partial-thickness tears, and full-thickness tears. Cross-sectional study; Level of evidence, 3. Patients undergoing surgical management for GTPS, in isolation or as an ancillary procedure during hip arthroscopy for femoroacetabular impingement, between April 2008 and February 2020 were included. Of these, 85 procedures were isolated treatment of GTPS and the remaining 628 were ancillary to hip arthroscopy. Radiographs were scrutinized for the presence of pertrochanteric calcifications. The hip abductor tendon status was intraoperatively classified as intact, partial-thickness tear, or full-thickness tear. The prevalence and correlation of the various radiographic findings in relation to the intraoperatively classified tendon condition were analyzed via the odds ratio (OR). Surgery was performed on 713 hips with recalcitrant GTPS. No tear was found in 340 hips (47.7%), 289 hips (40.5%) had a partial-thickness tear, and 84 hips (11.8%) had a full-thickness tear. Radiographically, 102 hips (14.3%) demonstrated proximally directed enthesophytes, and 34 (4.8%) had distally directed enthesophytes. In addition, 75 hips (10.5%) had amorphous calcifications, 47 (6.6%) had isolated ossicles, and 110 (15.4%) had surface irregularities. The presence of any calcification was associated with partial-thickness tears (OR, 1.67 [95% CI, 1.21-2.21]; P = .002) and full-thickness tears (OR, 6.40 [95% CI, 3.91-10.47]; P < .001). Distally directed enthesophytes (OR, 10.18 [95% CI, 3.08-33.63]; P < .001) and proximally directed enthesophytes (OR, 8.69 [95% CI, 4.66-16.21]; P < .001) were the findings with the highest OR for the presence of any type of tear. Distally directed enthesophytes were the findings with the highest OR for a full-thickness tear (OR, 15.79 [95% CI, 7.55-33.06]; P < .001). Isolated ossicles were the findings with the highest OR for a partial-thickness tear (OR, 1.73 [95% CI, 0.96-3.13]; P = .070). Pertrochanteric calcifications were common radiographic findings in patients with GTPS and can help guide management in these patients. Proximally and distally directed enthesophytes were strong predictors for the presence of a hip abductor tendon tear, and specifically a full-thickness tear, and increasing size of the findings was associated with more severe tendon injuries.


Impact of shift work on cardiovascular functions in a 10-year follow-up study.
The purpose of this study was to determine whether shift work affects the heart-rate-adjusted QT interval (QTc) in electorcardiography (ECG) and the blood pressure of workers without overt cardiovascular dysfunction. At a copper smelter, 158 shift workers and 75 day workers who underwent an ECG examination and blood pressure measurements in 1986 were followed for 10 years. In 1996, biochemical indicators such as high-density lipoprotein cholesterol and triglycerides were measured, together with the QTc. In 1986 and 1996, the QTc was significantly longer in the shift workers than in the day workers. Of 180 workers with a normal QTc (<420 ms(1/2) in 1986, 15% had developed a prolonged QTc (420 ms(1/2) in 1996 (18% of the 117 shift workers and 11% of the 63 day workers). Among the workers with a normal QTc in 1986, the shift workers had a significantly longer QTc than the day workers when the QTc was examined in 1996. In addition, shift-day work in the group with a normal QTc was significantly related to the QTc in 1996 after control for age, work duration, biochemical indicators, smoking, and drinking habits. However, the blood pressures of the shift and day workers did not differ significantly, and in 1996 the values of both groups were significantly elevated. These data suggest that shift work is associated with QTc prolongation. This evidence may explain the increased risk for cardiovascular diseases due to shift work.


The implementation of the functional task exercise programme for elderly people living at home.
The Functional Task Exercise programme is an evidence-based exercise programme for elderly people living at home. It enhances physical capacity with sustainable effects. FTE is provided by physiotherapists and remedial therapists. Although the intervention was found to be effective in a Randomised Controlled Trial, we may not assume that therapists will automatically supply the programme or that elderly people will automatically join the programme. This study protocol focuses on identifying determinants of implementation, developing implementation strategies and studying the effects of the implementation in daily practice. Phase 1: The systematic identification of determinants of the implementation of FTE among therapists and the elderly. A questionnaire study was conducted in a random sample of 100 therapists, and interviews took place with 23 therapists and 8 elderly people (aged 66 to 80 years). The determinants were broken down into four categories: the characteristics of the environment, the organisation, the therapists, and the training programme.Phase 2: Developing and applying strategies adapted to the determinants identified. Fifteen physiotherapists will be trained to provide FTE and to recruit elderly people living at home. The therapists will then deliver the 12-week programme to two groups of elderly, each consisting of six to twelve people aged 70 years or older.Phase 3: Study of implementation and the impact. To study the actual use of FTE: 1) therapists record information about the selection of participants and how they apply the key features of FTE, 2) the participating elderly will keep an exercise logbook, 3) telephone interviews will take place with the therapists and the elderly and there will be on-site visits. The effects on the elderly people will be studied using: 1) the Patient-Specific Questionnaire, the Timed Up and Go test and a two performance tests. All tests will be performed at the start of the FTE programme, half way through, and at the end of the programme. The number of older people will increase in many countries in the years to come and so the project outcomes will be of interest to policy-makers, insurance companies, health-care professionals and implementation researchers.


A population-based study on alcohol and high-risk sexual behaviors in Botswana.
In Botswana, an estimated 24% of adults ages 15-49 years are infected with HIV. While alcohol use is strongly associated with HIV infection in Africa, few population-based studies have characterized the association of alcohol use with specific high-risk sexual behaviors. We conducted a cross-sectional, population-based study of 1,268 adults from five districts in Botswana using a stratified two-stage probability sample design. Multivariate logistic regression was used to assess correlates of heavy alcohol consumption (>14 drinks/week for women, and >21 drinks/week for men) as a dependent variable. We also assessed gender-specific associations between alcohol use as a primary independent variable (categorized as none, moderate, problem and heavy drinking) and several risky sex outcomes including: (a) having unprotected sex with a nonmonogamous partner; (b) having multiple sexual partners; and (c) paying for or selling sex in exchange for money or other resources. Criteria for heavy drinking were met by 31% of men and 17% of women. Adjusted correlates of heavy alcohol use included male gender, intergenerational relationships (age gap > or =10 y), higher education, and living with a sexual partner. Among men, heavy alcohol use was associated with higher odds of all risky sex outcomes examined, including unprotected sex (AOR = 3.48; 95% confidence interval [CI], 1.65 to 7.32), multiple partners (AOR = 3.08; 95% CI, 1.95 to 4.87), and paying for sex (AOR = 3.65; 95% CI, 2.58 to 12.37). Similarly, among women, heavy alcohol consumption was associated with higher odds of unprotected sex (AOR = 3.28; 95% CI, 1.71 to 6.28), multiple partners (AOR = 3.05; 95% CI, 1.83 to 5.07), and selling sex (AOR = 8.50; 95% CI, 3.41 to 21.18). A dose-response relationship was seen between alcohol use and risky sexual behaviors, with moderate drinkers at lower risk than both problem and heavy drinkers. Alcohol use is associated with multiple risks for HIV transmission among both men and women. The findings of this study underscore the need to integrate alcohol abuse and HIV prevention efforts in Botswana and elsewhere.


Metal ion sensing novel calix[4]crown fluoroionophore with a two-photon absorption property.
1,3-Alternate calix[4]arene-based fluorescent chemosensors bearing two-photon absorbing chromophores have been synthesized, and their sensing behaviors toward metal ions were investigated via absorption band shifts as well as one- and two-photon fluorescence changes. Free ligands absorb the light at 461 nm and weakly emit their fluorescence at 600 nm when excited by UV-vis radiation at 461 nm, but no two-photon excited fluorescence is emitted by excitation at 780 nm. Addition of an Al(3+) or Pb(2+) ion to a solution of the ligand causes a blue-shifted absorption and enhanced fluorescence due to a declined resonance energy transfer (RET) upon excitation by one- and two-photon processes. Addition of a Pb(2+) ion to a solution of 1.K(+) results in a higher fluorescence intensity than the original 1.Pb(2+) complex regardless of one- or two-photon excitation, due to the allosteric effect induced by the complexation of K(+) with a crown loop.


On recursion.
It is a truism that conceptual understanding of a hypothesis is required for its empirical investigation. However, the concept of recursion as articulated in the context of linguistic analysis has been perennially confused. Nowhere has this been more evident than in attempts to critique and extend Hauseretal's. (2002) articulation. These authors put forward the hypothesis that what is uniquely human and unique to the faculty of language-the faculty of language in the narrow sense (FLN)-is a recursive system that generates and maps syntactic objects to conceptual-intentional and sensory-motor systems. This thesis was based on the standard mathematical definition of recursion as understood by Gödel and Turing, and yet has commonly been interpreted in other ways, most notably and incorrectly as a thesis about the capacity for syntactic embedding. As we explain, the recursiveness of a function is defined independent of such output, whether infinite or finite, embedded or unembedded-existent or non-existent. And to the extent that embedding is a sufficient, though not necessary, diagnostic of recursion, it has not been established that the apparent restriction on embedding in some languages is of any theoretical import. Misunderstanding of these facts has generated research that is often irrelevant to the FLN thesis as well as to other theories of language competence that focus on its generative power of expression. This essay is an attempt to bring conceptual clarity to such discussions as well as to future empirical investigations by explaining three criterial properties of recursion: computability (i.e., rules in intension rather than lists in extension); definition by induction (i.e., rules strongly generative of structure); and mathematical induction (i.e., rules for the principled-and potentially unbounded-expansion of strongly generated structure). By these necessary and sufficient criteria, the grammars of all natural languages are recursive.


Invariant NKT cell response to dengue virus infection in human.
Dengue viral infection is a global health threat without vaccine or specific treatment. The clinical outcome varies from asymptomatic, mild dengue fever (DF) to severe dengue hemorrhagic fever (DHF). While adaptive immune responses were found to be detrimental in the dengue pathogenesis, the roles of earlier innate events remain largely uninvestigated. Invariant natural killer T (iNKT) cells represent innate-like T cells that could dictate subsequent adaptive response but their role in human dengue virus infection is not known. We hypothesized that iNKT cells play a role in human dengue infection. Blood samples from a well-characterized cohort of children with DF, DHF, in comparison to non-dengue febrile illness (OFI) and healthy controls at various time points were studied. iNKT cells activation were analyzed by the expression of CD69 by flow cytometry. Their cytokine production was then analyzed after α-GalCer stimulation. Further, the CD1d expression on monocytes, and CD69 expression on conventional T cells were measured. iNKT cells were activated during acute dengue infection. The level of iNKT cell activation associates with the disease severity. Furthermore, these iNKT cells had altered functional response to subsequent ex vivo stimulation with α-GalCer. Moreover, during acute dengue infection, monocytic CD1d expression was also upregulated and conventional T cells also became activated. iNKT cells might play an early and critical role in the pathogenesis of severe dengue viral infection in human. Targeting iNKT cells and CD1d serve as a potential therapeutic strategy for severe dengue infection in the future.


Nandrolone decanoate interferes with testosterone biosynthesis altering blood-testis barrier components.
The aim of this study was to investigate whether nandrolone decanoate (ND) use affects testosterone production and testicular morphology in a model of trained and sedentary mice. A group of mice underwent endurance training while another set led a sedentary lifestyle and were freely mobile within cages. All experimental groups were treated with either ND or peanut oil at different doses for 6 weeks. Testosterone serum levels were measured via liquid chromatography-mass spectrometry. Western blot analysis and quantitative real-time PCR were utilized to determine gene and protein expression levels of the primary enzymes implicated in testosterone biosynthesis and gene expression levels of the blood-testis barrier (BTB) components. Immunohistochemistry and immunofluorescence were conducted for testicular morphological evaluation. The study demonstrated that moderate to high doses of ND induced a diminished serum testosterone level and altered the expression level of the key steroidogenic enzymes involved in testosterone biosynthesis. At the morphological level, ND induced degradation of the BTB by targeting the tight junction protein-1 (TJP1). ND stimulation deregulated metalloproteinase-9, metalloproteinase-2 (MMP-2) and the tissue inhibitor of MMP-2. Moreover, ND administration resulted in a mislocalization of mucin-1. In conclusion, ND abuse induces a decline in testosterone production that is unable to regulate the internalization and redistribution of TJP1 and may induce the deregulation of other BTB constituents via the inhibition of MMP-2. ND may well be considered as both a potential inducer of male infertility and a potential risk factor to a low endogenous bioavailable testosterone.


Hearing in caterpillars of the monarch butterfly (Danaus plexippus).
Many species of caterpillars have been reported to respond to sound, but there has been limited formal study of what sounds they hear, how they hear them and how they respond to them. Here, we report on hearing in caterpillars of the monarch butterfly (Danaus plexippus). Fourth and fifth instar caterpillars respond to sounds by freezing, contracting, and flicking their thorax in a vertical direction. Behavioural responses were evoked by sound frequencies between 50 and 900 Hz, with best sensitivity at 100-200 Hz. The lowest mean threshold was 79 dB SPL (particle velocity 605 μm s-1) at 150 Hz. When presented with a repeated 200 Hz sound tone, caterpillars habituate by no longer responding. A series of ablation experiments confirmed that the primary sensory receptors are a pair of long hairs, called trichoid sensilla, located on the upper prothorax. These sensilla are ∼450 µm long, rest in a socket and are innervated by a single bipolar sensory neuron. Removal of these setae reduced responses significantly compared with controls. Other setae contributed minimally to hearing in response to 200 Hz tones, and tubercles and prothoracic shields played no apparent role in sound reception. We propose that hearing functions to prevent attacks by aerial insect predators and parasitoids, which produce flight sounds in the frequency range to which the caterpillars are sensitive. This research lays the foundation for further investigations on the function and evolution of hearing in caterpillars, and has significance for the conservation of threatened monarch butterfly larvae living near noisy urban environments and roadways.


Involvement of Nox2 NADPH oxidase in retinal neovascularization.
The proliferation of new blood vessels in the retina is a leading cause of vision impairment. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox) is involved in cell signaling for ischemia-induced angiogenesis, but its role in retinal neovascularization is unclear. We have analyzed the dependence of retinal neovascularization on the Nox2 isoform in oxygen-induced retinopathy (OIR) in mice. Neonatal C57BL/6 mice aged 7 days (P7) were placed in a hyperoxic chamber (75% O2) for 5 days, followed by 5 days of exposure to room air. Eyes were harvested on P8 and P17 for the quantification of retinal vaso-obliteration and neovascularization, respectively. The retinal expression of Nox2 and VEGF-A were measured by RT-PCR, while superoxide generation was detected by in situ dihydroethidium (DHE) staining of fresh frozen sections. In wild type (WT) mice, OIR was characterized by central retinal vaso-obliteration at P8 and neovascularization at P17, which was associated with increases in Nox2 and VEGF-A gene expression, superoxide generation, and accumulation of Iba-1 positive cells in the inner retina. In contrast, Nox2 knockout mice exhibited markedly less retinal neovascularization and VEGF-A mRNA expression at P17, despite showing comparable vaso-obliteration at P8. These changes were accompanied by reductions in DHE fluorescence and Iba-1-positive cell accumulation in the hypoxic retina. The Nox2-generated reactive oxygen species (ROS) facilitate the retinal expression of VEGF-A and neovascularization in this mouse model of OIR. Therapies targeting Nox2 could be of value to reduce aberrant retinal neovascularization in retinopathy of prematurity, diabetes, and other disease processes driven by VEGF.