Quantitative proteomic profiling reveals novel region-specific markers in the adult mouse brain.
Despite major advances in neuroscience, a comprehensive understanding of the structural and functional components of the adult brain compartments remains to be fully elucidated at a quantitative molecular level. Indeed, over half of the soluble- and membrane-annotated proteins are currently unmapped within online digital brain atlases. In this study, two complementary approaches were used to assess the unique repertoire of proteins enriched within select regions of the adult mouse CNS, including the brain stem, cerebellum, and remaining brain hemispheres. Of the 1200 proteins visualized by 2D-DIGE, approximately 150 (including cytosolic and membrane proteins) were found to exhibit statistically significant changes in relative abundance thus representing putative region-specific brain markers. In addition to using a high-precision (18) O-labeling strategy for the quantitative LC-MS/MS mapping of membrane proteins isolated from myelin-enriched fractions, we have identified over 1000 proteins that have yet to be described in any other mammalian myelin proteome. A comparison of our myelin proteome was made to an existing transcriptome database containing mRNA abundance profiles during oligodendrocyte differentiation and has confirmed statistically significant abundance changes for ∼500 of these newly mapped proteins, thus revealing new roles in oligodendrocyte and myelin biology. These data offer a resource for the neuroscience community studying the molecular basis for specialized neuronal activities in the CNS and myelin-related disorders. The MS proteomics data associated with this manuscript have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000327 (http://proteomecentral.proteomexchange.org/dataset/PXD000327).


Comparative finite element analysis of the cranial performance of four herbivorous marsupials.
Marsupial herbivores exhibit a wide variety of skull shapes and sizes to exploit different ecological niches. Several studies on teeth, dentaries, and jaw adductor muscles indicate that marsupial herbivores exhibit different specializations for grazing and browsing. No studies, however, have examined the skulls of marsupial herbivores to determine the relationship between stress and strain, and the evolution of skull shape. The relationship between skull morphology, biomechanical performance, and diet was tested by applying the finite element method to the skulls of four marsupial herbivores: the common wombat (Vombatus ursinus), koala (Phascolarctos cinereus), swamp wallaby (Wallabia bicolor), and red kangaroo (Macropus rufus). It was hypothesized that grazers, requiring stronger skulls to process tougher food, would have higher biomechanical performance than browsers. This was true when comparing the koala and wallaby (browsers) to the wombat (a grazer). The cranial model of the wombat resulted in low stress and high mechanical efficiency in relation to a robust skull capable of generating high bite forces. However, the kangaroo, also a grazer, has evolved a very different strategy to process tough food. The cranium is much more gracile and has higher stress and lower mechanical efficiency, but they adopt a different method of processing food by having a curved tooth row to concentrate force in a smaller area and molar progression to remove worn teeth from the tooth row. Therefore, the position of the bite is crucial for the structural performance of the kangaroo skull, while it is not for the wombat which process food along the entire tooth row. In accordance with previous studies, the results from this study show the mammalian skull is optimized to resist forces generated during feeding. However, other factors, including the lifestyle of the animal and its environment, also affect selection for skull morphology to meet multiple functional demands.


Antitumor therapeutic application of self-assembled RNAi-AuNP nanoconstructs: Combination of VEGF-RNAi and photothermal ablation.
Nucleic acid-directed self-assembly provides an attractive method to fabricate prerequisite nanoscale structures for a wide range of technological applications due to the remarkable programmability of DNA/RNA molecules. In this study, exquisite RNAi-AuNP nanoconstructs with various geometries were developed by utilizing anti-VEGF siRNA molecules as RNAi-based therapeutics in addition to their role as building blocks for programmed self-assembly. In particular, the anti-VEGF siRNA-functionalized AuNP nanoconstructs can take additional advantage of gold-nanoclusters for photothermal cancer therapeutic agent. A noticeable technical aspect of self-assembled RNAi-AuNP nanoconstructs in this study is the precise conjugation and separation of designated numbers of therapeutic siRNA onto AuNP to develop highly sophisticated RNA-based building blocks capable of creating various geometries of RNAi-AuNP nano-assemblies. The therapeutic potential of RNAi-AuNP nanoconstructs was validated in vivo as well as in vitro by combining heat generation capability of AuNP and anti-angiogenesis mechanism of siRNA. This strategy of combining anti-VEGF mechanism for depleting angiogenesis process at initial tumor progression and complete ablation of residual tumors with photothermal activity of AuNP at later tumor stage showed effective tumor growth inhibition and tumor ablation with PC-3 tumor bearing mice.


The 110-kD protein-calmodulin complex of the intestinal microvillus is an actin-activated MgATPase.
The microvillus 110-kD protein-calmodulin complex (designated 110K-CM) shares several properties with all myosins. In addition to its well-defined ATP-dependent binding interaction with F-actin, 110K-CM is an ATPase with diagnostically myosin-like divalent cation sensitivity. It exhibits maximum enzymatic activity in the presence of K+ and EDTA (0.24 mumol P1/mg per min) or in the presence of Ca++ (0.40 mumol P1/mg per min) and significantly less activity in physiological ionic conditions of salt and Mg++ (0.04 mumol P1/mg per min). This MgATPase is activated by F-actin in an actin concentration-dependent manner (up to 2.5-3.5-fold). The specific MgATPase activity of 110K-CM is also enhanced by the addition of 5-10 microM Ca++, but in the isolated complex, there is often also a decrease in the extent of actin activation in this range of free Ca++. Actin activation is maintained, however, in samples with exogenously added calmodulin; under these conditions, there is an approximately sevenfold stimulation of 110K-CM's enzymatic activity in the presence of 5-10 microM Ca++ and actin. 110K-CM is relatively indiscriminant in its nucleoside triphosphate specificity; in addition to ATP, GTP, CTP, UTP, and ITP are all hydrolyzed by the complex in the presence of either Mg++ or Ca++. Neither AMP nor the phosphatase substrate p-nitrophenyl phosphate are substrates for the enzymatic activity. The pH optimum for CaATPase activity is 6.0-7.5; maximum actin activation of MgATPase occurs over a broad pH range of 6.5-8.5. Finally, like myosins, purified 110K-CM crosslinks actin filaments into loosely ordered aggregates in the absence of ATP. Collectively these data support the proposal of Collins and Borysenko (1984, J. Biol. Chem., 259:14128-14135) that the 110K-CM complex is functionally analogous to the mechanoenzyme myosin.


[Expected and unexpected adverse events in the therapeutic endoscopy of the bile duct (ERCP): experience of a private national center in 1356 consecutive cases (1999-2008)].
We report our experience of 10 years in therapeutic procedures of the bile duct (ERCP), describing adverse events or major and minor complications. We describe the associated factors, management, and risk age groups. We comment on the measures taken to prevent and treat them. The reported complications are pancreatitis, perforation, sub-cutaneous emphysema, pneumoperitoneum, pneumomediastinum, pneumothorax and exceptionally sub capsular liver hematoma. We report the particulars of the proceedings. The total number of complications was 54 cases (3.98% of 1356 interventions). The Acute pancreatitis PA was the most common complication in 39 cases (2.88% of the total and 72% of complications). The 79.49% of the PA was mild. 82% of the PA occurs in women.The procedure related mortality was 1 case (0.007%).


Genetic identification of two sibling species of Lutzomyia longipalpis (Diptera: Psychodidae) that produce distinct male sex pheromones in Sobral, Ceará State, Brazil.
Lutzomyia longipalpis, the main sandfly vector for New World visceral leishmaniasis is a complex of an as yet undefined number of sibling species. At present, there is no consensus on the status (single species vs. species complex) of Brazilian populations. We applied five microsatellite loci to test the hypothesis that L. longipalpis occurs as two sympatric cryptic species in Sobral, Ceará State, Brazil as predicted by male sex pheromone chemotypes described previously for field specimens from this site [S-9-methyl-germacrene-B (9MGB) and a cembrene compound]. Abdominal spot morphology corresponds with pheromone type at this locality (9MGB in '1 spot' males and cembrene in '2 spot' males). Genotype data from 190 wild-caught L. longipalpis specimens collected in October 1999 and April 2001 were used to estimate genetic differentiation between the two sex pheromone populations and sampling dates. No significant (P > 0.05) genetic differences were found between the 1999 and 2001 9MGB samples (theta = 0.018; RST = -0.005), and genetic differentiation was low between the cembrene collections (theta = 0.037, P < 0.05; RST = -0.043, P > 0.05). By contrast, highly divergent allelic frequencies (largely at two microsatellite loci) corresponded to significant (P > 0.05) genetic differentiation (theta = 0.221; RST = 0.215) for all comparisons between samples with different pheromones. When pheromone samples were pooled across sample date, genetic differentiation was high (theta = 0.229; P < 0.001; Nem = 0.84). The allele frequency distribution at each of the five microsatellite loci was similar for males and females from the two collection years. Two of these loci showed highly divergent allele frequencies in the two sex pheromone populations. This was reflected in the highly significant genetic differentiation obtained from the male genotypes, between populations producing different pheromones (theta = 0.229-0.268; P < 0.0001 for the 2001 and theta = 0.254-0.558; P < 0.0001 for the 1999 collections, respectively). Similar results were obtained when the females, assigned to a pheromone type, were included in the analysis. Both a Bayesian analysis of the data set and a population assignment test provided strong evidence for two distinct populations corresponding to pheromone type. Given its genotype, the probability of assigning a 9MGB male to the original 9MGB population was 100% once the two years' collections were pooled. For cembrene-producing '2 spot' males this probability although still high, was lower than for 9MGB males, at 86%. This microsatellite data together with previously reported reproductive isolation between the two Sobral populations confirm that premating barriers are important in speciation of L. longipalpis.


Commercially funded and United States-based research is more likely to be published; good-quality studies with negative outcomes are not.
Prior studies implying associations between receipt of commercial funding and positive (significant and/or pro-industry) research outcomes have analyzed only published papers, which is an insufficiently robust approach for assessing publication bias. In this study, we tested the following hypotheses regarding orthopaedic manuscripts submitted for review: (1) nonscientific variables, including receipt of commercial funding, affect the likelihood that a peer-reviewed submission will conclude with a report of a positive study outcome, and (2) positive outcomes and other, nonscientific variables are associated with acceptance for publication. All manuscripts about hip or knee arthroplasty that were submitted to The Journal of Bone and Joint Surgery, American Volume, over seventeen months were evaluated to determine the study design, quality, and outcome. Analyses were carried out to identify associations between scientific factors (sample size, study quality, and level of evidence) and study outcome as well as between non-scientific factors (funding source and country of origin) and study outcome. Analyses were also performed to determine whether outcome, scientific factors, or nonscientific variables were associated with acceptance for publication. Two hundred and nine manuscripts were reviewed. Commercial funding was not found to be associated with a positive study outcome (p = 0.668). Studies with a positive outcome were no more likely to be published than were those with a negative outcome (p = 0.410). Studies with a negative outcome were of higher quality (p = 0.003) and included larger sample sizes (p = 0.05). Commercially funded (p = 0.027) and United States-based (p = 0.020) studies were more likely to be published, even though those studies were not associated with higher quality, larger sample sizes, or lower levels of evidence (p = 0.24 to 0.79). Commercially funded studies submitted for review were not more likely to conclude with a positive outcome than were nonfunded studies, and studies with a positive outcome were no more likely to be published than were studies with a negative outcome. These findings contradict those of most previous analyses of published (rather than submitted) research. Commercial funding and the country of origin predict publication following peer review beyond what would be expected on the basis of study quality. Studies with a negative outcome, although seemingly superior in quality, fared no better than studies with a positive outcome in the peer-review process; this may result in inflation of apparent treatment effects when the published literature is subjected to meta-analysis.


Medical image segmentation using watershed segmentation with texture-based region merging.
The use of the watershed algorithm for image segmentation is widespread because it is able to produce a complete division of the image. However, it is susceptible to over-segmentation and in medical image segmentation, this meant that that we do not have good representations of the anatomy. We address this issue by thresholding the gradient magnitude image and performing post-segmentation merging on the initial segmentation map. The automated thresholding technique is based on the histogram of the gradient magnitude map while the post-segmentation merging is based on the similarity in textural features (namely angular second moment, contrast, entropy and inverse difference moment) belonging to two neighboring partitions. When applied to the segmentation of various facial anatomical structures from magnetic resonance (MR) images, the proposed method achieved an overlap index of 92.6% compared to manual contour tracings. It is able to merge more than 80% of the initial partitions, which indicates that a large amount of over-segmentation has been reduced. Results produced using watershed algorithm with and without the proposed and proposed post-segmentation merging are presented for comparisons.


Role of serotonin in the hepato-gastroIntestinal tract: an old molecule for new perspectives.
Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis. Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut may open new therapeutic strategies in hepato-gastrointestinal diseases.


Toxicity of blue led light and A2E is associated to mitochondrial dynamics impairment in ARPE-19 cells: implications for age-related macular degeneration.
Age-related macular degeneration (AMD) is a multifactorial retinal disease characterized by a progressive loss of central vision. Retinal pigment epithelium (RPE) degeneration is a critical event in AMD. It has been associated to A2E accumulation, which sensitizes RPE to blue light photodamage. Mitochondrial quality control mechanisms have evolved to ensure mitochondrial integrity and preserve cellular homeostasis. Particularly, mitochondrial dynamics involve the regulation of mitochondrial fission and fusion to preserve a healthy mitochondrial network. The present study aims to clarify the cellular and molecular mechanisms underlying photodamage-induced RPE cell death with particular focus on the involvement of defective mitochondrial dynamics. Light-emitting diodes irradiation (445 ± 18 nm; 4.43 mW/cm2) significantly reduced the viability of both unloaded and A2E-loaded human ARPE-19 cells and increased reactive oxygen species production. A2E along with blue light, triggered apoptosis measured by MC540/PI-flow cytometry and activated caspase-3. Blue light induced mitochondrial fusion/fission imbalance towards mitochondrial fragmentation in both non-loaded and A2E-loaded cells which correlated with the deregulation of mitochondria-shaping proteins level (OPA1, DRP1 and OMA1). To our knowledge, this is the first work reporting that photodamage causes mitochondrial dynamics deregulation in RPE cells. This process could possibly contribute to AMD pathology. Our findings suggest that the regulation of mitochondrial dynamics may be a valuable strategy for treating retinal degeneration diseases, such as AMD.


A randomized controlled clinical trial to compare the safety and efficacy of edaravone in acute ischemic stroke.
Edaravone has potent antioxidant and free radical scavenger properties. Few Japanese studies had demonstrated its neuroprotective role in acute ischemic stroke (AIS). This study aims to evaluate the efficacy of edaravone in terms of functional outcome in a group of Indian patients of AIS. Fifty patients of AIS were randomly divided into two groups. The study group received 30 mg of edaravone twice daily for 14 days by infusion, while control group received normal saline infusion as placebo. Outcome assessment was done by the Modified Rankin Scale (MRS). MRS score ≤2 at 90 days was considered as a favorable outcome. Of 25 patients, 18 (72%) had favorable outcomes (MRS ≤2) at 90 days in edaravone group, while 10 (40%) of 25 patients in placebo group had favorable outcome (P < 0.005). Two patients expired (one in each group) during treatment. The mean Barthel index increased from 41.20 ± 32.70 at baseline to 82.40 ± 18.32 at day 90 in edaravone group as compared with placebo group in which scores were 44.20 ± 22.76 at baseline and 68.20 ± 21.30 at day 90 (P < 0.005). We therefore conclude that edaravone effectively improves functional outcome in AIS.


Control of IL-17 receptor signaling and tissue inflammation by the p38α-MKP-1 signaling axis in a mouse model of multiple sclerosis.
T helper 17 (T(H)17) cells, a subset of CD4+ T cells that secrete the proinflammatory cytokine interleukin-17 (IL-17), play a key pathogenic role in autoimmune diseases. Through inducible and tissue-specific deletion systems, we described the time- and tissue-specific roles of the mitogen-activated protein kinase (MAPK) p38α in mediating T(H)17 cell-induced tissue inflammation. Inducible deletion of Mapk14 (which encodes p38α) after the onset of experimental autoimmune encephalomyelitis (EAE), a murine model for human multiple sclerosis, protected mice from inflammation. Furthermore, the severity of EAE was markedly reduced in mice with specific loss of p38α in neuroectoderm-derived cells, including astrocytes, an effect that was associated with defective production of chemokines and decreased infiltration of the target tissue by immune cells. p38α linked IL-17 receptor (IL-17R) signaling to the expression of genes encoding proinflammatory chemokines and cytokines. Mice that lacked MAPK phosphatase 1 (MKP-1), an inhibitor of p38α, had exacerbated EAE and enhanced expression of IL-17R-dependent genes. Our results suggest that the p38α-MKP-1 signaling axis links IL-17R signaling in tissue-resident cells to autoimmune inflammation dependent on infiltrating T(H)17 cells.


Effectiveness of training in guideline-oriented biopsychosocial management of low-back pain in occupational health services - a cluster randomized controlled trial.
This study aimed to investigate the effectiveness of brief training in the guideline-oriented biopsychosocial management of low-back pain (LBP) in occupational health services using a cluster-randomized design. A small sample of physiotherapists and physicians from the intervention units (N=12) were given three- to seven-day training focusing on the biopsychosocial management of LBP, while professionals in the control units (N=15) received no such training. Eligible patients with LBP, with or without radicular pain, aged 18-65, were invited to participate. A web-based questionnaire was sent to all recruited patients at baseline, three months and one year. The primary outcome measure was disability (Oswestry Disability Index, ODI) over one year. Between-group differences were analyzed using linear and generalized linear mixed models adjusted for baseline-response delay as well as variables showing between-group imbalance at baseline. The final study sample comprised 234 and 81 patients in the intervention and control groups, respectively at baseline, and 137 and 47 patients, respectively, at one year. At baseline, the mean duration of pain was longer in the intervention group (P=0.017), and pain-related fear concerning physical activity was lower (P=0.012). We observed no significant difference between the groups' primary outcome measure (adjusted one-year mean difference in the ODI: 2.3; 95% confidence interval -1.0-5.7; P=0.175) or most secondary outcomes. Brief training in guideline-oriented biopsychosocial management of LBP for occupational health professionals did not appear to be effective in reducing patients' symptom over one-year follow-up compared to treatment as usual.


Web and Mobile Based HIV Prevention and Intervention Programs Pros and Cons - A Review.
With the increasing growth of HIV positive people the use of information and communication technologies (ICT) can play an important role in controlling the spread of the AIDS. Web and Mobile are the new technologies that young people take advantage from them. In this study a review to investigate the web and mobile based HIV prevention and intervention programs was carried out. A scoping review was conducted including PubMed, Science direct, Web of Science and Proquest to find relevant sources that published in 2009 to 2016. To identify published, original research that reported the web and mobile-based HIV prevention and intervention programs, an organized search was conducted with the following search keywords in combination: HIV, AIDS, m-Health, Mobile phone, Cell phone, Smartphone, Mobile health, internet, and web. Using the employed strategies, 173 references retrieved. Searched articles were compared based on their titles and abstracts. To identify duplicated articles, the title and abstracts were considered and 101 duplicated references were excluded. By going through the full text of related papers, 35 articles were found to be more related to the questions of this paper from which 72 final included. The advantages of web and mobile-based interventions include the possibility to provide constancy in the delivery of an intervention, impending low cost, and the ability to spread the intervention to an extensive community. Online programs such as Chat room-based Education program, Web-based therapeutic education system, and Online seek information can use for HIV/AIDS prevention. To use of mobile for HIV/AIDS prevention and intervention, programs including in: Health system focused applications, Population health focused applications, and Health messaging can be used.


A polymorphism of the renin gene rs6682082 is associated with essential hypertension risk and blood pressure levels in Korean women.
The aim of the present study was to investigate associations between the renin gene (REN) and the risk of essential hypertension and blood pressure (BP) levels in Koreans. To outline the functional role of a single nucleotide polymorphism in the transcription of the REN gene, we conducted a case-control study of 1975 individuals: 646 hypertension (HT) patients and 1329 ethnically and age-matched normotensive subjects. Logistic regression analysis indicated that the genotypes AA/AG were strongly associated with risk of HT (odds ratio, 1.493; 95% confidence interval, 1.069-2.086, p=0.018) in female subjects. The genotypes AA/AG also showed significant association with higher blood pressure levels, both systolic and diastolic, in postmenopausal HT women (p=0.003 and p=0.017, respectively). Analysis of the promoter containing rs6682082 revealed a 2.4±0.01-fold higher activity in the A variant promoter than the G variant promoter, suggesting that rs6682082 is itself a functional variant. We suggest that the A allele of rs6682082 is a positive genetic marker for predisposition to essential hypertension and high BP in Korean women and may be mediated through the transcriptional activation of REN.


Pflacco: Feature-Based Landscape Analysis of Continuous and Constrained Optimization Problems in Python.
The herein proposed Python package pflacco provides a set of numerical features to characterize single-objective continuous and constrained optimization problems. Thereby, pflacco addresses two major challenges in the area optimization. Firstly, it provides the means to develop an understanding of a given problem instance, which is crucial for designing, selecting, or configuring optimization algorithms in general. Secondly, these numerical features can be utilized in the research streams of automated algorithm selection and configuration. While the majority of these landscape features is already available in the R package flacco, our Python implementation offers these tools to an even wider audience and thereby promotes research interests and novel avenues in the area of optimization.


Preliminary analysis of the transmission dynamics of nosocomial infections: stochastic and management effects.
A simple mathematical model is developed for the spread of hand-borne nosocomial pathogens such as Staphylococcus aureus within a general medical-surgical ward. In contrast to previous models a stochastic approach is used. Computer simulations are used to explore the properties of the model, and the results are presented in terms of the pathogen's successful introduction rate, ward-level prevalence, and colonized patient-days, emphasizing the general effects of changes in management of patients and carers. Small changes in the transmissibility of the organism resulted in large changes in all three measures. Even small increases in the frequency of effective handwashes were enough to bring endemic organisms under control. Reducing the number of colonized patients admitted to the ward was also an effective control measure across a wide range of different situations. Increasing surveillance activities had little effect on the successful introduction rate but gave an almost linear reduction in colonized patient-days and ward-level prevalence. Shorter lengths of patient stay were accompanied by higher successful introduction rates, but had little effect on the other measures unless the mean time before detection of a colonized individual was large compared to the mean length of stay. We conclude that chance effects are likely to be amongst the most important factors in determining the course of an outbreak. Mathematical models can provide valuable insights into the non-linear interactions between a small number of processes, but for the very small populations found in hospital wards, a stochastic approach is essential.


Blocking of carbon nanotube based nanoinjectors by lipids: a simulation study.
Carbon nanotubes (CNTs) are possible nanoinjectors for the introduction of therapeutic agents into cells. To explore their interactions with a lipid bilayer membrane and to model the nanoinjection process, we used coarse-grained molecular dynamics to simulate the penetration of dipalmitoylphosphatidylcholine (DPPC) bilayers by single-walled CNTs. Lipids are extracted from a bilayer during CNT penetration and reside on both the inner and the outer tube surfaces. Lipids that interact with the CNT interior wall spread out and hence can "block" the tube. However, the degree of lipid lining of the inner surface is strongly dependent upon the tube penetration velocity, with fewer lipids extracted from the bilayer at higher rates. There is no apparent effect on bilayer integrity after CNT penetration, with the bilayer able to self-seal. Our findings reveal some of the complexities of the interactions of lipids with CNT nanoinjectors and suggest a need to further characterize the influence of, for example, CNT functionalization and cargo on lipid blocking of CNTs.


Assessing Caribbean Shallow and Mesophotic Reef Fish Communities Using Baited-Remote Underwater Video (BRUV) and Diver-Operated Video (DOV) Survey Techniques.
Fish surveys form the backbone of reef monitoring and management initiatives throughout the tropics, and understanding patterns in biases between techniques is crucial if outputs are to address key objectives optimally. Often biases are not consistent across natural environmental gradients such as depth, leading to uncertainty in interpretation of results. Recently there has been much interest in mesophotic reefs (reefs from 30-150 m depth) as refuge habitats from fishing pressure, leading to many comparisons of reef fish communities over depth gradients. Here we compare fish communities using stereo-video footage recorded via baited remote underwater video (BRUV) and diver-operated video (DOV) systems on shallow and mesophotic reefs in the Mesoamerican Barrier Reef, Caribbean. We show inconsistent responses across families, species and trophic groups between methods across the depth gradient. Fish species and family richness were higher using BRUV at both depth ranges, suggesting that BRUV is more appropriate for recording all components of the fish community. Fish length distributions were not different between methods on shallow reefs, yet BRUV recorded more small fish on mesophotic reefs. However, DOV consistently recorded greater relative fish community biomass of herbivores, suggesting that studies focusing on herbivores should consider using DOV. Our results highlight the importance of considering what component of reef fish community researchers and managers are most interested in surveying when deciding which survey technique to use across natural gradients such as depth.


Can family-centered programing mitigate HIV risk factors among orphaned and vulnerable adolescents? Results from a pilot study in South Africa.
Let's Talk is a structured, family-centered adolescent HIV prevention program developed for use in South Africa using key components adapted from programs successfully implemented in the US and South Africa. It is designed to address individual HIV transmission risk factors common among orphaned and vulnerable adolescents, including elevated risk for poor psychological health and sexual risk behavior. These efforts are accentuated through parallel programing to support caregivers' mental health and parenting skills. Twelve Let's Talk groups, each serving approximately 10 families, were piloted by two local community-based organizations in Gauteng and Kwa-Zulu Natal provinces, South Africa. Face-to-face interviews were conducted among participating caregivers and adolescents at baseline and three months post-intervention to explore the potential effects of the program on intermediate outcomes that may support HIV preventive behavior. Specifically, generalized estimation equations were used to estimate average change on HIV prevention knowledge and self-efficacy, caregiver and adolescent mental health, and family dynamics. Among the 105 adolescents and their 95 caregivers who participated in Let's Talk and completed both surveys, statistically significant improvements were found for adolescents' HIV and condom use knowledge as well as condom negotiation self-efficacy, but not sexual refusal self-efficacy. Both caregivers and adolescents demonstrated significantly better mental health at post-test. Adolescent/caregiver connection and communication about healthy sexuality also improved. These preliminary results highlight the potential of HIV prevention interventions that engage caregivers alongside the vulnerable adolescents in their care to mitigate adolescent HIV risk factors. A more rigorous evaluation is warranted to substantiate these effects and identify their impact on adolescents' risk behavior and HIV incidence.


Domestic decision-making power, social support, and postpartum depression symptoms among immigrant and native women in Taiwan.
Domestic decision-making power is an integral part of women's empowerment. No study has linked domestic decision-making power and social support concurrently to postpartum depression and compared these between immigrant and native populations. The aim of this study was to examine domestic decision-making power and social support and their relationship to postpartum depressive symptoms among immigrant and native women in Taiwan. This cross-sectional survey included 190 immigrant and 190 native women who had delivered healthy babies during the past year in Taipei City. Depression was measured using the Edinburgh Postnatal Depression Scale, with a cutoff score of 10. Logistic regression was used to determine the factors associated with postpartum depression symptoms. Immigrant mothers had significantly higher prevalence of postpartum depression symptoms (41.1% vs. 8.4%) and had significantly lower levels of domestic decision-making power and social support than native mothers did. Logistic regression showed that insufficient family income was associated with an increased risk of postpartum depression symptoms, whereas social support and domestic decision-making power levels were associated negatively with postpartum depression symptoms. After accounting for these factors, immigrant women remained at higher risk of postpartum depression symptoms than native women did, odds ratio = 2.59, 95% CI [1.27, 5.28]. Domestic decision-making power and social support are independent protective factors for postpartum depression symptoms among immigrant and native women in Taiwan. Social support and empowerment interventions should be tested to discover whether they are able to prevent or alleviate postpartum depression symptoms, with special emphasis on immigrant mothers.


Separation of cellulose from industrial paper mill wastewater dried sludge using a commercial and cheap ionic liquid.
Industrial wastewaters and their treatment are now placed at the heart of the environmental concerns that industries face. Some research work has been carried out in order to limit the impact of these wastes on the environment as well as their costs. In this study, wastewater dehydrated sludge (55% wt. water content) from the paper industry was used to recover cellulose by using tetrakis(hydroxymethyl)phosphonium chloride, [P(CH2OH)4]Cl, ionic liquid as a solvent. The ionic liquid has shown remarkable results in terms of cellulose extraction in addition to its non-volatility and lower toxicity compared to organic volatile solvents. All cellulose, based on dry sludge, was recovered from the industrial dehydrated sludge with better operation conditions. The influence of temperature and the quantity of ionic liquid was preliminary studied in order to optimise the extraction conditions.


Fluorescence spectrum of 2-trifluoromethyl-1,1,1,2,4,4,5,5,5-nonafluoro-3-pentanone.
A perfluorinated ketone, 2-trifluoromethyl-1,1,1,2,4,4,5,5,5-nonafluoro-3-pentanone, has been investigated to determine several physical and spectroscopic properties. It was found to exhibit fluorescence similar to that of acetone, emitting over the 360-550 nm range with a peak near 420 nm when excited at 355 nm. This compound's emission is nearly unaffected over a wide range of temperature and pressure in an argon bath gas. Its fluorescence efficiency was found to be three times higher than that of acetone. Combined with low reactivity and thermal stability up to 500 degrees C, this makes the material an excellent tracer for spectroscopic measurement techniques.


Hepatoprotective Activity of Heptoplus on Isoniazid and Rifampicin Induced Liver Damage in Rats.
The present study is designed to evaluate the efficacy of heptoplus a polyherbal formulation as an oral supplementary agent for isoniazid and rifampicin induced hepatotoxicity in rats. 50 and 100 mg/kg of heptoplus supplement were fed orally to the rats along with isoniazid and rifampicin and compared to rats treated with 100 mg/kg Liv 52 standard drug. Rats treated with isoniazid and rifampicin suffered from severe oxidative stress by the virtue of free radicals induced lipid per oxidation. As a result abnormal index of serum biochemical markers for liver function and increased liver lysosomal enzymes activity was observed. However rats nourished with 100 mg/kg of heptoplus and Liv 52 protected the liver from oxidative damage by maintaining normal antioxidant profile status and restored normal serum liver biochemical markers. Increased liver lysosomal enzymes activity is prevented in the rats supplemented with heptoplus and Liv 52. Histopathological analysis also revealed severe vascular changes and lobular necrosis in the treatment of isoniazid and rifampicin. Heptoplus (100 mg/kg) and Liv 52 supplemented rats liver apparently revealed normal architecture of liver. This study confirms that heptoplus has liver protective activity against Isoniazid and Rifampicin induced liver injury in rats, in par with Liv 52.


One-pot sequential reaction to 2-substituted-phenanthridinones from N-methoxybenzamides.
The sequential use of a hypervalent iodine reagent leads to the one-pot synthesis of 2-bromo/chloro-phenanthridinones via an amidation of arenes followed by a regioselective halogenation reaction. These consecutive C-H functionalization reactions can be used efficiently to construct 2-substituted-phenanthridinones at room temperature with good to high yields. Application of the current method is highlighted by the concise synthesis of the natural product PJ34.


Video-rate terahertz interferometric and synthetic aperture imaging.
Experimental results from a video-rate terahertz interferometric imaging system are presented. The source emits continuous narrow bandwidth radiation at 0.1 THz. The 2D image of a point source is reconstructed at a rate of 16 ms per frame with a four-element detector array. The image resolution and quality are affected by the number of detectors, the configuration of the detection array, and how well the baselines are calibrated. Details of the hardware system and video-rate terahertz image are presented.


Semantic congruency and the Colavita visual dominance effect.
Participants presented with auditory, visual, or bimodal audiovisual stimuli in a speeded discrimination task, fail to respond to the auditory component of bimodal targets significantly more often than to the visual component, a phenomenon known as the Colavita visual dominance effect. Given that spatial and temporal factors have recently been shown to modulate the Colavita effect, the aim of the present study, was to investigate whether semantic congruency also modulates the effect. In the three experiments reported here, participants were presented with a version of the Colavita task in which the stimulus congruency between the auditory and visual components of the bimodal targets was manipulated. That is, the auditory and visual stimuli could refer to the same or different object (in Experiments 1 and 2) or audiovisual speech event (Experiment 3). Surprisingly, semantic/stimulus congruency had no effect on the magnitude of the Colavita effect in any of the experiments, although it exerted a significant effect on certain other aspects of participants' performance. This finding contrasts with the results of other recent studies showing that semantic/stimulus congruency can affect certain multisensory interactions.


Impact of geographic accessibility on utilization of the annual health check-ups by income level in Japan: A multilevel analysis.
Although both geographic accessibility and socioeconomic status have been indicated as being important factors for the utilization of health care services, their combined effect has not been evaluated. The aim of this study was to reveal whether an income-dependent difference in the impact of geographic accessibility on the utilization of government-led annual health check-ups exists. Existing data collected and provided by Chiba City Hall were employed and analyzed as a retrospective cohort study. The subjects were 166,966 beneficiaries of National Health Insurance in Chiba City, Japan, aged 40 to 74 years. Of all subjects, 54,748 (32.8%) had an annual health check-up in fiscal year 2012. As an optimal index of geographic accessibility has not been established, five measures were calculated: travel time to the nearest health care facility, density of health care facilities (number facilities within a 30-min walking distance from the district of residence), and three indices based on the two-step floating catchment area method. Three-level logistic regression modeling with random intercepts for household and district of residence was performed. Of the five measures, density of health care facilities was the most compatible according to Akaike's information criterion. Both low density and low income were associated with decreased utilization of the health check-ups. Furthermore, a linear relationship was observed between the density of facilities and utilization of the health check-ups in all income groups and its slope was significantly steeper among subjects with an equivalent income of 0.00 yen than among those with equivalent income of 1.01-2.00 million yen (p = 0.028) or 2.01 million yen or more (p = 0.040). This result indicated that subjects with lower incomes were more susceptible to the effects of geographic accessibility than were those with higher incomes. Thus, better geographic accessibility could increase the health check-up utilization and also decrease the income-related disparity of utilization.


Chondrocyte clocks make cartilage time-sensitive material.
Circadian rhythms mediated by both central and tissue-specific peripheral clocks allow for the synchronization of biological processes with diurnal cycles such as activity and rest. Disruption of these rhythms can be caused by altered sleep-awake patterns or by pathological conditions and can initiate or exacerbate human disease through mechanisms that are only partially understood. In this issue, Dudek et al. identify a chondrocyte-autonomous cartilage clock and demonstrate that expression of an important circadian pacemaker, BMAL1, decreases during osteoarthritis progression. They show that chondrocyte-specific deletion of BMAL1 leads to cartilage degradation and disruption of key pathways, shifting cartilage homeostasis toward a catabolic state. These findings provide insight into the interplay between circadian rhythm and cartilage in osteoarthritis.


Etiology of Bull's Eye Rot of Pear Caused by Neofabraea spp. in Oregon, Washington, and California.
A collection of Neofabraea isolates from pear fruit grown in Oregon, Washington, and California was screened with species-specific primers in a multiplex polymerase chain reaction (PCR). Neofabraea alba was identified most frequently in samples from Oregon and California, whereas N. perennans was found most frequently in samples from Washington. N. alba also was identified from tissue of small cankers and pruning stubs on pear trees using PCR. Bull's eye rot pathogens were isolated from fruit of nine different European pear cultivars, Asian pear, and quince. Overall, N. alba was the most prevalent species in 2001 whereas N. perennans was more prevalent in 2002. An undescribed species of Neofabraea was identified in samples from Medford, OR that corresponds to a species previously found by others using molecular methods. This information increases the known geographic distribution of this undescribed species.


Blame the Patient, Blame the Doctor or Blame the System? A Meta-Synthesis of Qualitative Studies of Patient Safety in Primary Care.
Studies of patient safety in health care have traditionally focused on hospital medicine. However, recent years have seen more research located in primary care settings which have different features compared to secondary care. This study set out to synthesize published qualitative research concerning patient safety in primary care in order to build a conceptual model. Meta-ethnography, an interpretive synthesis method whereby third order interpretations are produced that best describe the groups of findings contained in the reports of primary studies. Forty-eight studies were included as 5 discrete subsets where the findings were translated into one another: patients' perspectives of safety, staff perspectives of safety, medication safety, systems or organisational issues and the primary/secondary care interface. The studies were focused predominantly on issues seen to either improve or compromise patient safety. These issues related to the characteristics or behaviour of patients, staff or clinical systems and interactions between staff, patients and staff, or people and systems. Electronic health records, protocols and guidelines could be seen to both degrade and improve patient safety in different circumstances. A conceptual reading of the studies pointed to patient safety as a subjective feeling or judgement grounded in moral views and with potentially hidden psychological consequences affecting care processes and relationships. The main threats to safety appeared to derive from 'grand' systems issues, for example involving service accessibility, resources or working hours which may not be amenable to effective intervention by individual practices or health workers, especially in the context of a public health system. Overall, the findings underline the human elements in patient safety primary health care. The key to patient safety lies in effective face-to-face communication between patients and health care staff or between the different staff involved in the care of an individual patient. Electronic systems can compromise safety when they override the opportunities for face-to-face communication. The circumstances under which guidelines or protocols are seen to either compromise or improve patient safety needs further investigation.


TRPV4-Mediated Regulation of the Blood Brain Barrier Is Abolished During Inflammation.
Blood-brain barrier (BBB) dysfunction is critically involved in determining the extent of several central nervous systems (CNS) pathologies and here in particular neuroinflammatory conditions. Inhibiting BBB breakdown could reduce the level of vasogenic edema and the number of immune cells invading the CNS, thereby counteracting neuronal injury. Transient receptor potential (TRP) channels have an important role as environmental sensors and constitute attractive therapeutic targets that are involved in calcium homeostasis during pathologies of the CNS. Transient receptor potential vanilloid 4 (TRPV4) is a calcium permeable, non-selective cation channel highly expressed in endothelial cells. As it is involved in the regulation of the blood brain barrier permeability and consequently cerebral edema formation, we anticipated a regulatory role of TRPV4 in CNS inflammation and subsequent neuronal damage. Here, we detected an increase in transendothelial resistance in mouse brain microvascular endothelial cells (MbMECs) after treatment with a selective TRPV4 inhibitor. However, this effect was abolished after the addition of IFNγ and TNFα indicating that inflammatory conditions override TRPV4-mediated permeability. Accordingly, we did not observe a protection of Trpv4-deficient mice when compared to wildtype controls in a preclinical model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), and no differences in infarct sizes following transient middle cerebral artery occlusion (tMCAO), the experimental stroke model, which leads to an acute postischemic inflammatory response. Furthermore, Evans Blue injections did not show differences in alterations of the blood brain barrier (BBB) permeability between genotypes in both animal models. Together, TRPV4 does not regulate brain microvascular endothelial permeability under inflammation.


Effects of Stroke on the Autonomic Nervous System.
Stroke is the fourth leading cause of death in the United States and the second most common cause of death worldwide; stroke is also the leading cause of long-term disability worldwide. It is clear that the consequences of cerebral ischemia reach beyond the brain into the periphery, and a significant number of stroke related deaths are the result of conditions that develop poststroke in the periphery. The two leading causes of non-neurogenic death poststroke are cardiac abnormalities and infections. Changes in autonomic nervous system function that favor increased sympathetic nervous system activity and reduced parasympathetic nervous system activity appear to be causative factors in both conditions. Here, we review the evidence that sympathetic nervous system activity increases and parasympathetic nervous system activity declines poststroke. We discuss effects of autonomic dysfunction on cardiac arrhythmias and heart rate variability. Finally, we discuss the evidence supporting a role for autonomic dysfunction in the increased incidence of infection poststroke. Although the death rate from stroke is declining in the United States, the incidence of stroke is not. With more patients surviving the initial ischemic event it is important that we broaden our understanding of the chronic effects of stroke on the human condition.


Malignant and Nonmalignant Complications of the Rectal Stump in Patients with Inflammatory Bowel Disease.
Patients with refractory inflammatory bowel disease (IBD) might require a subtotal colectomy with construction of an ileostomy. Due to the risk of nerve damage and pelvic sepsis, the diverted rectum is often left in situ. Evidence on long-term complications of this rectal stump is limited, particularly in patients with Crohn's disease (CD). In addition to the risk of development of neoplasia, diversion proctitis is a frequently reported rectal stump associated complication. Surprisingly, clear recommendations concerning rectal stump surveillance and timing of proctectomy are lacking. Through the use of a pathology database and a review of medical records, we established a cohort of IBD patients with a diverted rectum. Among these patients, long-term complications of the rectal stump were identified. Main endpoint was advanced neoplasia (carcinoma or high-grade dysplasia [HGD]) in the rectal stump. Risk factors for advanced neoplasia were identified using Cox regression modeling. In the second, prospective part of the study, a questionnaire was sent out to 165 patients with either a rectal stump in situ or who had undergone a proctectomy, in order to identify differences in patient-reported outcome measures associated with the excision of the rectal stump. From 530 patients with IBD and a (temporal) diversion of the rectum, we included 250 patients in whom the rectal stump was left in situ for more than 12 months. The majority of patients was female (61%) and had Crohn's disease (67%). On follow-up (median 8 years), 8 carcinomas, 2 cases of high-grade dysplasia, and 7 cases of low-grade dysplasia were found with incidence rates of 3.9 and 8.5 per 1000 patient-years of follow-up for cancer and all neoplasia, respectively. The 8 cases of rectal stump cancer (RSC) were diagnosed after a median of 15 years after colectomy. A history of colorectal neoplasia was associated with advanced rectal stump neoplasia. Out of 191 patients with endoscopic follow-up, rectal stump inflammation occurred in 161 (88.5%) patients. Results of the questionnaire did not show a significant difference in quality of life between patients with and patients without a rectal stump, although the latter group reported significantly more sexual and urinary symptoms than patients with a rectal stump in situ. The majority of rectal stump patients reported rectal blood loss, but 65.5% of them were not or barely limited in daily life by their rectal stumprelated problems. Rectal stump cancer has a low incidence rate, with patients with a history of colonic neoplasia carrying the highest risk of developing this severe complication. We observed no significant differences in quality of life between rectal stump and postproctectomy patients, but proctectomy surgery is associated with sexual and urinary complications.


The essential tension between leadership and power: when leaders sacrifice group goals for the sake of self-interest.
Throughout human history, leaders have been responsible for helping groups attain important goals. Ideally, leaders use their power to steer groups toward desired outcomes. However, leaders can also use their power in the service of self-interest rather than effective leadership. Five experiments identified factors within both the person and the social context that determine whether leaders wield their power to promote group goals versus self-interest. In most cases, leaders behaved in a manner consistent with group goals. However, when their power was tenuous due to instability within the hierarchy, leaders high (but not low) in dominance motivation prioritized their own power over group goals: They withheld valuable information from the group, excluded a highly skilled group member, and prevented a proficient group member from having any influence over a group task. These self-interested actions were eliminated when the group was competing against a rival outgroup. Findings provide important insight into factors that influence the way leaders navigate the essential tension between leadership and power.


Engineering the cytokinin-glucoside specificity of the maize β-D-glucosidase Zm-p60.1 using site-directed random mutagenesis.
The maize β-D-glucosidase Zm-p60.1 releases active cytokinins from their storage/transport forms, and its over-expression in tobacco disrupts zeatin metabolism. The role of the active-site microenvironment in fine-tuning Zm-p60.1 substrate specificity has been explored, particularly in the W373K mutant, using site-directed random mutagenesis to investigate the influence of amino acid changes around the 373 position. Two triple (P372T/W373K/M376L and P372S/W373K/M376L) and three double mutants (P372T/W373K, P372S/W373K and W373K/M376L) were prepared. Their catalytic parameters with two artificial substrates show tight interdependence between substrate catalysis and protein structure. P372T/W373K/M376L exhibited the most significant effect on natural substrate specificity: the ratio of hydrolysis of cis-zeatin-O-β-D-glucopyranoside versus the trans-zeatin-O-β-D-glucopyranoside shifted from 1.3 in wild-type to 9.4 in favor of the cis- isomer. The P372T and M376L mutations in P372T/W373K/M376L also significantly restored the hydrolytic velocity of the W373K mutant, up to 60% of wild-type velocity with cis-zeatin-O-β-D-glucopyranoside. These findings reveal complex relationships among amino acid residues that modulate substrate specificity and show the utility of site-directed random mutagenesis for changing and/or fine-tuning enzymes. Preferential cleavage of specific isomer-conjugates and the capacity to manipulate such preferences will allow the development of powerful tools for detailed probing and fine-tuning of cytokinin metabolism in planta.


Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells.
Reverse engineering of gene regulatory networks can be used to predict regulatory interactions of an organism faced with environmental changes, but can prove problematic, especially when focusing on complicated multi-factorial processes. Candida albicans is a major human fungal pathogen. During the infection process, this fungus is able to adapt to conditions of very low iron availability. Such adaptation is an important virulence attribute of virtually all pathogenic microbes. Understanding the regulation of iron acquisition genes will extend our knowledge of the complex regulatory changes during the infection process and might identify new potential drug targets. Thus, there is a need for efficient modelling approaches predicting key regulatory events of iron acquisition genes during the infection process. This study deals with the regulation of C. albicans iron uptake genes during adhesion to and invasion into human oral epithelial cells. A reverse engineering strategy is presented, which is able to infer regulatory networks on the basis of gene expression data, making use of relevant selection criteria such as sparseness and robustness. An exhaustive use of available knowledge from different data sources improved the network prediction. The predicted regulatory network proposes a number of new target genes for the transcriptional regulators Rim101, Hap3, Sef1 and Tup1. Furthermore, the molecular mode of action for Tup1 is clarified. Finally, regulatory interactions between the transcription factors themselves are proposed. This study presents a model describing how C. albicans may regulate iron acquisition during contact with and invasion of human oral epithelial cells. There is evidence that some of the proposed regulatory interactions might also occur during oral infection. This study focuses on a typical problem in Systems Biology where an interesting biological phenomenon is studied using a small number of available experimental data points. To overcome this limitation, a special modelling strategy was used which identifies sparse and robust networks. The data is augmented by an exhaustive search for additional data sources, helping to make proposals on regulatory interactions and to guide the modelling approach. The proposed modelling strategy is capable of finding known regulatory interactions and predicts a number of yet unknown biologically relevant regulatory interactions.


Bora and the kinase Aurora a cooperatively activate the kinase Plk1 and control mitotic entry.
A central question in the study of cell proliferation is, what controls cell-cycle transitions? Although the accumulation of mitotic cyclins drives the transition from the G2 phase to the M phase in embryonic cells, the trigger for mitotic entry in somatic cells remains unknown. We report that the synergistic action of Bora and the kinase Aurora A (Aur-A) controls the G2-M transition. Bora accumulates in the G2 phase and promotes Aur-A-mediated activation of Polo-like kinase 1 (Plk1), leading to the activation of cyclin-dependent kinase 1 and mitotic entry. Mechanistically, Bora interacts with Plk1 and controls the accessibility of its activation loop for phosphorylation and activation by Aur-A. Thus, Bora and Aur-A control mitotic entry, which provides a mechanism for one of the most important yet ill-defined events in the cell cycle.


Epistasis and the sensitivity of phenotypic screens for beta thalassaemia.
Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low-income and lower-middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene-frequency estimates, to help ensure the optimal allocation of public health resources. For both of these functions it is vital that the screen performed is suitably sensitive. One popular first-stage screening option to detect carriers of beta thalassaemia in low-income countries is the One Tube Osmotic Fragility Test (OTOFT). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts. We demonstrate that interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose-6-phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of OTOFTs for beta thalassaemia heterozygosity to below 70%. Our results therefore caution against the widespread application of OTOFTs in regions where these erythrocyte variants co-occur.


Effect of sitagliptin on the working memory and reference memory in type 2 diabetic Sprague-Dawley rats: possible role of adiponectin receptors 1.
Type 2 diabetes mellitus (DM) is associated with increased incidence of behavioral changes and memory loss. Memory loss could be caused by Alzheimer's disease (AD) and vascular dementia (VaD). So, we aimed to investigate the effect of sitagliptin in improving the working and reference memories in diabetic rats. Thirty six male Sprague-Dawley rats divided equally (n=12) into three groups: control, type 2 DM and type 2 DM treated with DPP-4 inhibitor (sitagliptin) for one month (10 mg/kg) orally. Working memory and reference memory were assessed by using the holeboard memory test. In all rats, serum glucose, insulin, adiponectin, total cholesterol (TC), TG, low (LDL) and high (HDL) density lipoprotein with calculation of the homeostasis model of assessment-insulin resistance index (HOMA-IR) and atherogenic index. The hypothalamus was separated for determination of the acetylcholine level and adiponectin receptors 1 (Adipo R1) m-RNA expression. Type 2 diabetic rats exhibited a significant decrease in both working and reference memories, with increased glucose, insulin and HOMA-IR. The adiponectin level, acetylcholine content of the hypothalamus and Adipo R1 m-RNA expression were significantly reduced. Treatment with sitagliptin significantly improved the working and reference memories with significant reduction in the glucose, insulin and HOMA-IR. Moreover, sitagliptin increased significantly the acetylcholine content of the hypothalamus and Adipo R1 expression. In conclusion, sitagliptin might improve the cognitive function of the diabetic rats and the hypothalamic acetylcholine level possibly through increased AdipoR1 expression.


Association of paraoxonase-1(Q192R and L55M) gene polymorphisms and activity with colorectal cancer and effect of surgical intervention.
Colorectal cancer (CRC) is a leading cause of cancer-related death. Oxidative DNA damage may contribute to cancer risk and the antioxidant paraoxonase is one endogenous free radical scavenger in the human body which could therefore exert an influeence. Aim of this study was to determine the role of serum arylesterase (ARE) and paraoxonase 1(PON1) activities in CRC patients and to find any association between (PON1) Q192R and L55M gene polymorphisms in CRC patients. Also the serum ARE and PON1 activities in CRC patients will be investigated before and after surgery Materials and Methods: This study involved a total of 50 patients with newly diagnosed CRC and 80 healthy controls. PON1 and ARE activities were determined using an enzymatic spectrophotometric method. PON1 Q192R and L55M gene polymorphisms were determined using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based restriction fragment analysis. The restriction enzyme AlwI was used to examine the Q192R polymorphism and Hsp92II for the L55M polymorphism. Significant differences in the PON1 Q192R polymorphism were found between patients and controls. The Q allele was more frequent in the patient group than in controls, while the R allele was more frequent in the controls. Significant differences were found in the L55M polymorphism. Additionally, there were significant differences in L and M allele frequencies (p=0.001). The serum activities of PON1 and ARE were low in QQ and MM genotype. serum PON1 and ARE activities were significantly lower in CRC patients compared to healthy subjects. The R allele may protect against colorectal cancer.


The application of artificial intelligence (AI) techniques to identify frailty within a residential aged care administrative data set.
Research has shown that frailty, a geriatric syndrome associated with an increased risk of negative outcomes for older people, is highly prevalent among residents of residential aged care facilities (also called long term care facilities or nursing homes). However, progress on effective identification of frailty within residential care remains at an early stage, necessitating the development of new methods for accurate and efficient screening. We aimed to determine the effectiveness of artificial intelligence (AI) algorithms in accurately identifying frailty among residents aged 75 years and over in comparison with a calculated electronic Frailty Index (eFI) based on a routinely-collected residential aged care administrative data set drawn from 10 residential care facilities located in Queensland, Australia. A secondary objective included the identification of best-performing candidate algorithms. We designed a frailty prediction system based on the eFI identification of frailty, allocating 84.5 % and 15.5 % of the data to training and test data sets respectively. We compared the performance of 18 specific scenarios to predict frailty against eFI based on unique combinations of three ML algorithms (support vector machines [SVM], decision trees [DT] and K-nearest neighbours [KNN]) and six cases (6, 10, 11, 14, 39 and 70 input variables). We calculated accuracy, percentage positive and negative agreement, sensitivity, specificity, Cohen's kappa and Prevalence- and Bias- Adjusted Kappa (PABAK), table frequencies and positive and negative predictive values. Of 592 eligible resident records, 500 were allocated to the training set and 92 to the test set. Three scenarios (10, 11 and 70 input variables), all based on SVM algorithm, returned overall accuracy above 75 %. There is some potential for AI techniques to contribute towards better frailty identification within residential care. However, potential benefits will need to be weighed against administrative burden, data quality concerns and presence of potential bias.


Lung stereotactic body radiotherapy using a coplanar versus a non-coplanar beam technique: a comparison of clinical outcomes.
To determine if lung stereotactic body radiotherapy (SBRT) using a coplanar beam technique was associated with similar outcomes as lung SBRT using a non-coplanar beam technique. A retrospective review was performed of patients undergoing lung SBRT between January 2008 and April 2011. SBRT was initially delivered with multiple non-coplanar, non-overlapping beams; however, starting in December 2009, SBRT was delivered predominantly with all coplanar beams in order to reduce treatment time and complexity. This analysis included 149 patients; the median follow-up was 21 months. SBRT was delivered for primary (n = 90) or recurrent (n = 17) non-small cell lung cancer, or lung oligometastasis (n = 42). The most common dose (Gy)/fraction (fx) regimens were 48 Gy/4 fx (39%), 54 Gy/3 fx (37%), and 50 Gy/5 fx (17%). The beam arrangement was coplanar in 61 patients (41%) and non-coplanar in 88 patients (59%). In patients treated with 54 Gy/3 fx, the mean treatment times per fraction for the coplanar and non-coplanar cohorts were 10 and 14 minutes (p < 0.0001). Kaplan-Meier 2-year estimates of overall survival (OS), progression-free survival, and local control (LC) for the coplanar and non-coplanar cohorts were 65% vs. 56% (p = 0.30), 47% vs. 39% (p = 0.71), and 92% and 92% (p = 0.94), respectively. The 1-year estimates of grade 2-5 pulmonary toxicity for the coplanar and non-coplanar cohorts were 11% and 17%, respectively (p = 0.30). On multivariate analysis, beam arrangement was not significantly associated with OS, LC or pulmonary toxicity. Patients treated with lung SBRT using a coplanar technique had similar outcomes as those treated with a non-coplanar technique.


A follow-up study of high-functioning autistic children.
It is well known that IQ is an important prognostic variable in the outcome of autistic children. There are, however, very few data available on the outcome of nonretarded autistic children as adults. We identified 16 such probands from records and followed them up between 11 and 27 years since discharge from a center specializing in the assessment of autistic children. There were 12 males and 4 females, average age was 26, and mean IQ was 92 (range 68-110). Although the majority were functioning poorly in terms of occupational-social outcome and psychiatric symptoms, a surprising number (4) had a very good outcome and might be considered recovered. The severity of early autistic behavior was a poor predictor of outcome, but neuropsychologic measures of nonverbal problem solving were highly correlated with outcomes. The results of the study indicate that a small percentage of nonretarded autistic children can be expected to recover to a substantial degree.


Induction of CD8+ T cells using heterologous prime-boost immunisation strategies.
One of the current challenges in vaccine design is the development of antigen delivery systems or vaccination strategies that induce high protective levels of CD8+ T cells. These cells are crucial for protection against certain tumours and intracellular pathogens such as the liver-stage parasite of malaria. A liver-stage malaria vaccine should therefore include CD8+ T-cell-inducing components. This review provides an overview of prime-boost immunisation strategies that result in protective CD8+ T-cell responses against malaria with an emphasis on work from our laboratory. Possible mechanisms explaining why heterologous prime-boost strategies, in particular boosting with replication-impaired recombinant poxviruses, are so effective are discussed.


Incidence and outcomes of heparin-induced thrombocytopenia in solid malignancy: an analysis of the National Inpatient Sample Database.
Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction to heparin products characterized by thrombocytopenia with or without thrombosis. This study aimed to determine the incidence, morbidity, mortality and economic burden of HIT in solid-malignancy-related hospitalizations. We analyzed the National Inpatient Sample Database (NIS), the largest public database of hospital admissions in the United States, from January 2012 to September 2015. The primary outcome of the study was the incidence of HIT. Secondary outcomes included incidence of venous thrombosis (acute deep venous thrombosis and pulmonary embolism), arterial thrombosis (thrombotic stroke, myocardial infarctions and other arterial thromboembolism), mortality associated with HIT, length of stay, total hospital charges and disposition. During the study period, 7 437 049 hospitalizations had an associated diagnosis of solid malignancy. Approximately 0·08% (n = 6225) hospitalizations had a secondary diagnosis of HIT in this population. The standardized incidence of total thrombotic events was higher in the solid malignancy with HIT compared to the solid malignancy without HIT group (24·7% vs. 6·8%, P < 0·001). The standardized mortality rate was 4·8% in solid malignancy with HIT compared to 3·4% in the without HIT group (OR, 1·53; 95% CI, 1·25-1·89; P < 0·001). HIT in solid malignancy is a rare condition but associated with increased morbidity and mortality.


Efficacy of the LiSN & Learn auditory training software: randomized blinded controlled study.
Children with a spatial processing disorder (SPD) require a more favorable signal-to-noise ratio in the classroom because they have difficulty perceiving sound source location cues. Previous research has shown that a novel training program - LiSN & Learn - employing spatialized sound, overcomes this deficit. Here we investigate whether improvements in spatial processing ability are specific to the LiSN & Learn training program. Participants were ten children (aged between 6;0 [years;months] and 9;9) with normal peripheral hearing who were diagnosed as having SPD using the Listening in Spatialized Noise - Sentences test (LiSN-S). In a blinded controlled study, the participants were randomly allocated to train with either the LiSN & Learn or another auditory training program - Earobics - for approximately 15 min per day for twelve weeks. There was a significant improvement post-training on the conditions of the LiSN-S that evaluate spatial processing ability for the LiSN & Learn group (P=0.03 to 0.0008, η(2)=0.75 to 0.95, n=5), but not for the Earobics group (P=0.5 to 0.7, η(2)=0.1 to 0.04, n=5). Results from questionnaires completed by the participants and their parents and teachers revealed improvements in real-world listening performance post-training were greater in the LiSN & Learn group than the Earobics group. LiSN & Learn training improved binaural processing ability in children with SPD, enhancing their ability to understand speech in noise. Exposure to non-spatialized auditory training does not produce similar outcomes, emphasizing the importance of deficit-specific remediation.


The intricate association of COVID-19 pandemic with ecological issues.
This critical narrative review is intended to emphasize the comprehensive ecological issues related to the evolution of the novel coronavirus, the environmental factors associated with the disease progress, and the impact the pandemic is having on the environment. Approximately 60% of the emerging infectious disease of the last century (including deadly viruses like HIV, Ebola, Influenza, coronavirus strains like SARS, MERS) are linked to zoonotic spillover. Therefore, to escape the emergence of newer cross-species infections, proper precautionary measures should be taken. Every country has specific rules to deal with the biomedical waste produced in hospitals. But the COVID-19 pandemic has posed a unique global challenge due to the overwhelming amount of biomedical waste generated from dedicated COVID hospitals, diagnostic facilities, quarantine centers, and home quarantine facilities. Moreover, inappropriate disposal of masks by the general public may contaminate the environment turning it into a potential health hazard. Therefore, strict adherence to Biomedical Waste Management Guidelines for proper disposal of masks and other medical waste by all concerned is a must. Lockdown has brought about tremendous improvement in conditions of the world's atmosphere, hydrosphere, and biosphere. Dramatic improvement in air quality index, decrease in water, and noise pollution are some of the positive aspects of lockdown. However, these effects are temporary. But these teach an important lesson to the world to take some permanent measures to bring down greenhouse gases and other toxic emissions. Some harmful effects of lockdown are illegal deforestation, wildlife trafficking, encroachment of reserved areas etc.


Progress in research on childhood T-cell acute lymphocytic leukemia, Notch1 signaling pathway, and its inhibitors: A review.
Childhood leukemia is cancer that seriously threatens the life of children in China. Poor sensitivity to chemotherapy and susceptibility to drug resistance are the reasons for the treatment of T-cell acute lymphocytic leukemia (T-ALL) being extremely difficult. Moreover, traditional intensive chemotherapy regimens cause great damage to children. Therefore, it is highly important to search for targeted drugs and develop a precise individualized treatment for child patients. There are activating mutations in the NOTCH1 gene in more than 50% of human T-ALLs and the Notch signaling pathway is involved in the pathogenesis of T-ALL. In this review, we summarize the progress in research on T-ALL and Notch1 signaling pathway inhibitors to provide a theoretical basis for the clinical treatment of T-ALL.


Measuring salient food attitudes and food-related values. An elaborated, conflicting and interdependent system.
Consumer food choice behaviour in post-industrial countries is complex and influenced by a multitude of interacting variables. This study looked at the antecedents of behaviour and examined salient food-related values and attitudes. To discover personal meanings and patterns of everyday food choices across different situations we used a qualitative approach in the form of repertory grid interviews. An analysis of the personal constructs elicited from a representative sample of 100 Swiss consumers revealed elaborated value systems. The food-related values can be summarised as: authenticity/naturalness, conviviality, health, quality/indulgence, convenience, and price. The salience of these values and their negatively evaluated counterparts differed for various social eating situations and product categories. Consumers' personal values also differed significantly from their perception of current trends in eating culture. In every-day food choices interdependent food-related values compete and are thus a possible cause of ambivalence and conflicts. The findings offer explanations of discrepancies between values/attitudes and behaviour that may be due to situational constraints and habits. Implications for companies include the need for strategic realignment to regain consumers' trust by providing comprehensive value-congruent food solutions that also consider health and ethical criteria.


Denitrification and anammox: Understanding nitrogen loss from Yangtze Estuary to the east China sea (ECS).
The Yangtze River, which is the largest in Euro-Asian, receives tremendous anthropogenic nitrogen input and is typically characterized by severe eutrophication and hypoxia. Two major processes, denitrification and anaerobic ammonium oxidation (anammox), play vital roles for removing nitrogen global in nitrogen cycling. In the current study, sediment samples were collected from both latitudinal and longitudinal transects along the coastal Yangtze River and the East China Sea (ECS). We investigated community composition and distributions of nosZ gene-encoded denitrifiers by high throughput sequencing, and also quantified the relative abundances of both denitrifying and anammox bacteria by q-PCR analysis. Denitrifying communities showed distinct spatial distribution patterns that were impacted by physical (water current and river runoffs) and chemical (nutrient availability and organic content) processes. Both denitrifying and anammox bacteria contributed to the nitrogen removal in Yangtze Estuary and the adjacent ECS, and these two processes shifted from coastal to open ocean with reverse trends: the abundance of nosZ gene decreased from coastal to open ocean while anammox exhibited an increasing trend based on quantifications of hzsB and 16S rRNA genes. Further correspondence correlation analysis revealed that salinity and nutrients were the main factors in structuring composition and distribution of denitrifying and anammox bacteria. This study improved our understanding of dynamic processes in nitrogen removal from estuarine to open ocean. We hypothesize that denitrification is the major nitrogen removal pathway in estuaries, but in open oceans, low nutrient and organic matter concentrations restrict denitrification, thus increasing the importance of anammox as a nitrogen removal process.


Molecular surveillance of low pathogenic avian influenza viruses in wild birds across the United States: inferences from the hemagglutinin gene.
A United States interagency avian influenza surveillance plan was initiated in 2006 for early detection of highly pathogenic avian influenza viruses (HPAIV) in wild birds. The plan included a variety of wild bird sampling strategies including the testing of fecal samples from aquatic areas throughout the United States from April 2006 through December 2007. Although HPAIV was not detected through this surveillance effort we were able to obtain 759 fecal samples that were positive for low pathogenic avian influenza virus (LPAIV). We used 136 DNA sequences obtained from these samples along with samples from a public influenza sequence database for a phylogenetic assessment of hemagglutinin (HA) diversity in the United States. We analyzed sequences from all HA subtypes except H5, H7, H14 and H15 to examine genetic variation, exchange between Eurasia and North America, and geographic distribution of LPAIV in wild birds in the United States. This study confirms intercontinental exchange of some HA subtypes (including a newly documented H9 exchange event), as well as identifies subtypes that do not regularly experience intercontinental gene flow but have been circulating and evolving in North America for at least the past 20 years. These HA subtypes have high levels of genetic diversity with many lineages co-circulating within the wild birds of North America. The surveillance effort that provided these samples demonstrates that such efforts, albeit labor-intensive, provide important information about the ecology of LPAIV circulating in North America.


A silviculture application of the glyphosate-based herbicide VisionMAX to wetlands has limited direct effects on amphibian larvae.
Herbicides are commonly used in agriculture and silviculture to reduce interspecific competition among plants and thereby enhance crop growth, quality, and volume. Internationally, glyphosate-based herbicides are the most widely used herbicides in both of these sectors. Laboratory and mesocosm studies have demonstrated that some formulations are toxic to amphibian larvae below concentrations that approximate predicted maximal or "worst-case" exposure scenarios. However, field studies have not found evidence of toxicity at these concentrations. The authors conducted a replicated field experiment involving 10 naturalized wetlands split in half with an impermeable plastic barrier to assess the direct toxicity of a glyphosate formulation commonly used in silviculture (VisionMAX™). The herbicide formulation was applied directly to the surface of one side of each wetland at one of two target aqueous exposure rates (high = 2,880, low = 550 µg acid equivalents [a.e.]/L), and the other side was left as an untreated control. The survival and growth of green frog larvae (Lithobates clamitans) were assessed for two years following herbicide treatment. The herbicide did not have a negative impact on survival or growth of L. clamitans larvae at either treatment level. In fact, mean larval abundance was typically greater in the treated sides than in control sides within the year of herbicide application. These results indicate that typical silviculture use of VisionMAX poses negligible risk to larval amphibians, likely because the combined effects of sorption and degradation in natural wetlands limit the exposure magnitude and duration.


miRNA-1236 inhibits HIV-1 infection of monocytes by repressing translation of cellular factor VprBP.
Primary monocytes are refractory to HIV-1 infection and become permissive upon differentiation into monocyte-derived dendritic cells (MDDCs) or macrophages. Multiple mechanisms have been proposed to interpret HIV-1 restriction in monocytes. Human cellular miRNAs can modulate HIV-1 infection by targeting either conserved regions of the HIV-1 genome or host gene transcripts. We have recently reported that the translation of host protein pur-alpha is repressed by abundant cellular miRNAs to inhibit HIV-1 infection in monocytes. Here, we report that the transcript of another cellular factor, VprBP [Vpr (HIV-1)-binding protein], was repressed by cellular miRNA-1236, which contributes to HIV-1 restriction in monocytes. Transfection of miR-1236 inhibitors enhanced translation of VprBP in monocytes and significantly promoted viral infection; exogenous input of synthesized miR-1236 mimics into MDDCs suppressed translation of VprBP, and, accordingly, significantly impaired viral infection. Our data emphasize the role of miRNA in modulating differentiation-dependent susceptibility of the host cell to HIV-1 infection. Understanding the modulation of HIV-1 infection by cellular miRNAs may provide key small RNAs or the identification of new important protein targets regulated by miRNAs for the development of antiviral strategies.


Effects of ceftiofur and chlortetracycline treatment strategies on antimicrobial susceptibility and on tet(A), tet(B), and bla CMY-2 resistance genes among E. coli isolated from the feces of feedlot cattle.
A randomized controlled field trial was conducted to evaluate the effects of two sets of treatment strategies on ceftiofur and tetracycline resistance in feedlot cattle. The strategies consisted of ceftiofur crystalline-free acid (CCFA) administered to either one or all of the steers within a pen, followed by feeding or not feeding a therapeutic dose of chlortetracycline (CTC). Eighty-eight steers were randomly allocated to eight pens of 11 steers each. Both treatment regimens were randomly assigned to the pens in a two-way full factorial design. Non-type-specific (NTS) E. coli (n = 1,050) were isolated from fecal samples gathered on Days 0, 4, 12, and 26. Antimicrobial susceptibility profiles were determined using a microbroth dilution technique. PCR was used to detect tet(A), tet(B), and bla CMY-2 genes within each isolate. Chlortetracycline administration greatly exacerbated the already increased levels of both phenotypic and genotypic ceftiofur resistance conferred by prior CCFA treatment (P<0.05). The four treatment regimens also influenced the phenotypic multidrug resistance count of NTS E. coli populations. Chlortetracycline treatment alone was associated with an increased probability of selecting isolates that harbored tet(B) versus tet(A) (P<0.05); meanwhile, there was an inverse association between finding tet(A) versus tet(B) genes for any given regimen (P<0.05). The presence of a tet(A) gene was associated with an isolate exhibiting reduced phenotypic susceptibility to a higher median number of antimicrobials (n = 289, median = 6; 95% CI = 4-8) compared with the tet(B) gene (n = 208, median = 3; 95% CI = 3-4). Results indicate that CTC can exacerbate ceftiofur resistance following CCFA therapy and therefore should be avoided, especially when considering their use in sequence. Further studies are required to establish the animal-level effects of co-housing antimicrobial-treated and non-treated animals together.


[The anti-arrhythmia effect and hemodynamic effects of Bonnecor in intravenous administration].
For testing the efficiency of Bonnecor in intravenous administration (0.3 mg/kg) 36 patients were examined electrophysiologically (31 with paroxysmal supraventricular tachycardias, 5 with ventricular tachycardias). In other 6 patients haemodynamic investigations were performed by means of right-heart catheterization and thermodilution. The supraventricular tachycardias induced by programmed electrostimulation could be interrupted by administration of Bonnecor in 45% of the cases. After the administration of Bonnecor the inducibility of supraventricular tachycardias was suppressed in 11 of the 31 patients. In 2 of the 5 patients with ventricular tachycardia an evocation of ventricular tachycardias was no more possible after an intravenous application of Bonnecor; a medicamentous termination of the ventricular tachycardias had been tried only in one case. Clinically relevant negatively inotropic effects could not be proved. Apart from insignificant malaises in few cases, no side-effects occurred.


Anti-Inflammatory Activity of Citric Acid-Treated Wheat Germ Extract in Lipopolysaccharide-Stimulated Macrophages.
Until recently, fermentation was the only processing used to improve the functionality of wheat germ. The release of 2,6-dimethoxy-1,4-benzoquinone (DMBQ) from hydroquinone glycosides during the fermentation process is considered a marker of quality control. Here, we treated wheat germ extract with citric acid (CWG) to release DMBQ and examined the anti-inflammatory activity of this extract using a lipopolysaccharide-activated macrophage model. Treatment of wheat germ with citric acid resulted in detectable release of DMBQ but reduced total phenolic and total flavonoid contents compared with untreated wheat germ extract (UWG). CWG inhibited secretion of the pro-inflammatory cytokines tumor necrosis factor-α, interleukin (IL)-6, and IL-12 and the synthesis of cyclooxygenase-2, while UWG only decreased IL-12 production. CWG and UWG induced high levels of anti-inflammatory IL-10 and heme oxygenase-1. CWG specifically inhibited phosphorylation of NF-κB p65 and p38 kinase at 15 min after LPS stimulation. Our study showed that citric acid treatment enhanced the anti-inflammatory activity of wheat germ extract.


Identification of a genetic cluster influencing memory performance and hippocampal activity in humans.
Experimental work in animals has shown that memory formation depends on a cascade of molecular events. Here we show that variability of human memory performance is related to variability in genes encoding proteins of this signaling cascade, including the NMDA and metabotrobic glutamate receptors, adenylyl cyclase, CAMKII, PKA, and PKC. The individual profile of genetic variability in these signaling molecules correlated significantly with episodic memory performance (P < 0.00001). Moreover, functional MRI during memory formation revealed that this genetic profile correlated with activations in memory-related brain regions, including the hippocampus and parahippocampal gyrus. The present study indicates that genetic variability in the human homologues of memory-related signaling molecules contributes to interindividual differences in human memory performance and memory-related brain activations.


Visual Analytics for Comparison of Ocean Model Output with Reference Data: Detecting and Analyzing Geophysical Processes Using Clustering Ensembles.
Researchers assess the quality of an ocean model by comparing its output to that of a previous model version or to observations. One objective of the comparison is to detect and to analyze differences and similarities between both data sets regarding geophysical processes, such as particular ocean currents. This task involves the analysis of thousands or hundreds of thousands of geographically referenced temporal profiles in the data. To cope with the amount of data, modelers combine aggregation of temporal profiles to single statistical values with visual comparison. Although this strategy is based on experience and a well-grounded body of expert knowledge, our discussions with domain experts have shown that it has two limitations: (1) using a single statistical measure results in a rather limited scope of the comparison and in significant loss of information, and (2) the decisions modelers have to make in the process may lead to important aspects being overlooked. In this article, we propose a Visual Analytics approach that broadens the scope of the analysis, reduces subjectivity, and facilitates comparison of the two data sets. It comprises three steps: First, it allows modelers to consider many aspects of the temporal behavior of geophysical processes by conducting multiple clusterings of the temporal profiles in each data set. Modelers can choose different features describing the temporal behavior of relevant processes, clustering algorithms, and parameterizations. Second, our approach consolidates the clusterings of one data set into a single clustering via a clustering ensembles approach. The consolidated clustering presents an overview of the geospatial distribution of temporal behavior in a data set. Third, a visual interface allows modelers to compare the two consolidated clusterings. It enables them to detect clusters of temporal profiles that represent geophysical processes and to analyze differences and similarities between two data sets. This work is the result of a close collaboration with ocean modelers. They employed our concept to find aspects of improvement in a new version of the Ocean Model for Circulation and Tides (OMCT).


Gel-based protease proteomics for identifying the novel calpain substrates in dopaminergic neuronal cell.
Calpains are a family of calcium-dependent cysteine proteases that are ubiquitously expressed in mammals and play critical roles in neuronal death by catalyzing substrate proteolysis. Here, we developed two-dimensional gel electrophoresis-based protease proteomics to identify putative calpain substrates. To accomplish this, cellular lysates from neuronal cells were first separated by pI, and the immobilized sample on a gel strip was incubated with a recombinant calpain and separated by molecular weight. Among 25 altered protein spots that were differentially expressed by at least 2-fold, we confirmed that arsenical pump-driving ATPase, optineurin, and peripherin were cleaved by calpain using in vitro and in vivo cleavage assays. Furthermore, we found that all of these substrates were cleaved in MN9D cells treated with either ionomycin or 1-methyl-4-phenylpyridinium, both of which cause a calcium-mediated calpain activation. Their cleavage was blocked by calcium chelator or calpain inhibitors. In addition, calpain-mediated cleavage of these substrates and its inhibition by calpeptin were confirmed in a middle cerebral artery occlusion model of cerebral ischemia, as well as a stereotaxic brain injection model of Parkinson disease. Transient overexpression of each protein was shown to attenuate 1-methyl-4-phenylpyridinium-induced cell death, indicating that these substrates may confer protection of varying magnitudes against dopaminergic injury. Taken together, the data indicate that our protease proteomic method has the potential to be applicable for identifying proteolytic substrates affected by diverse proteases. Moreover, the results described here will help us decipher the molecular mechanisms underlying the progression of neurodegenerative disorders where protease activation is critically involved.


Current and former ecstasy users report different sleep to matched controls: a web-based questionnaire study.
This study sought to test the association between ecstasy-use and abnormal sleep. An anonymous web-based questionnaire containing questions on drug use and sleep was completed by 1035 individuals. From this large sample, a group of 89 ecstasy users were found who reported very little use of other drugs. This "ecstasy-only" group was further divided into two groups of 31 current users and 58 abstinent users. The subjective sleep of current and former ecstasy-only users was compared with that of matched controls. Patients were asked to rate their sleep according to: 1) sleep quality, 2) sleep latency, 3) night time awakenings and 4) total sleep time. Current ecstasy-only users reported significantly worse sleep quality (P < 0.05) and a greater total sleep time (P < 0.001) than controls. It was inferred that these differences might be due to recovery from the acute effects of the drug. Abstinent ecstasy-only users reported significantly more nighttime awakenings than controls (P < 0.01). These subjective findings are in agreement with the objective findings of previous studies showing persistent sleep abnormalities in ecstasy users.


Thermal biology, microhabitat selection, and conservation of the insular lizard Podarcis hispanica atrata.
We studied aspects of the thermal biology and microhabitat selection of the endangered lizard Podarcis hispanica atrata during autumn in the field and laboratory. Body temperatures (T b ) of active lizards were within a narrow range, were largely independent of ambient temperatures, and exhibited little diel variation. Activity T b s largely coincided with the selected temperatures maintained in a laboratory thermogradient and with T b s that maximize running performance. Alternation of basking with other activities and shuttling between sun and shade were obvious aspects of thermoregulatory behaviour. Lizards shifted microhabitat use throughout the day. During early morning and late afternoon, basking lizards were restricted to rocky sites surrounded by shrubs. Near midday lizards used a wider array of microhabitats, and many moved in open grassy sites. Juveniles maintained lower activity T b s, had lower selected temperatures, and basked less frequently than the adults. Juveniles occupied open grassy patches more often than the adults. We discuss the relevance of our results for the conservation of this extremely rare lizard and the management of its habitats.