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1.  A RIAM/lamellipodin–talin–integrin complex forms the tip of sticky fingers that guide cell migration 
Nature Communications  2015;6:8492.
The leading edge of migrating cells contains rapidly translocating activated integrins associated with growing actin filaments that form ‘sticky fingers' to sense extracellular matrix and guide cell migration. Here we utilized indirect bimolecular fluorescence complementation to visualize a molecular complex containing a Mig-10/RIAM/lamellipodin (MRL) protein (Rap1-GTP-interacting adaptor molecule (RIAM) or lamellipodin), talin and activated integrins in living cells. This complex localizes at the tips of growing actin filaments in lamellipodial and filopodial protrusions, thus corresponding to the tips of the ‘sticky fingers.' Formation of the complex requires talin to form a bridge between the MRL protein and the integrins. Moreover, disruption of the MRL protein–integrin–talin (MIT) complex markedly impairs cell protrusion. These data reveal the molecular basis of the formation of ‘sticky fingers' at the leading edge of migrating cells and show that an MIT complex drives these protrusions.
The leading edge of migrating cells contains activated integrins associated with growing actin filaments that form ‘sticky fingers' to guide cell migration. Here, the authors detect a complex of MRL proteins, talin and activated integrins in lamellipodia and filopodia in living cells, comprising the tips of the ‘sticky fingers'.
PMCID: PMC4589889  PMID: 26419705
2.  A RIAM/Lamellipodin-Talin-Integrin Complex Forms the Tip of Sticky Fingers That Guide Cell Migration 
Nature communications  2015;6:8492.
The leading edge of migrating cells contains rapidly translocating activated integrins associated with growing actin filaments that form "sticky fingers" that sense extracellular matrix and guide cell migration. Here we utilized indirect bimolecular fluorescence complementation (BiFC) to visualize a molecular complex containing an MRL protein (RIAM or lamellipodin), talin, and activated integrins in living cells. This complex localizes at the tips of growing actin filaments in lamellipodial and filopodial protrusions, thus corresponding to the tips of the "sticky fingers." Formation of the complex requires talin to form a bridge between the MRL protein and the integrins. Moreover, disruption of the MRL protein-integrin-talin (MIT) complex markedly impairs cell protrusion. These data reveal the molecular basis of the formation of "sticky fingers" at the leading edge of migrating cells and show that an MIT complex drives these protrusions.
PMCID: PMC4589889  PMID: 26419705
3.  Texture perception through direct and indirect touch: An analysis of perceptual space for tactile textures in two modes of exploration 
Somatosensory & motor research  2007;24(1-2):53-70.
Considerable information about the texture of objects can be perceived remotely through a probe. It is not clear, however, how texture perception with a probe compares with texture perception with the bare finger. Here we investigate the perception of a variety of textured surfaces encountered daily (e.g., corduroy, paper, and rubber) using the two scanning modes—direct touch through the finger and indirect touch through a probe held in the hand—in two tasks. In the first task, subjects rated the overall pair-wise dissimilarity of the textures. In the second task, subjects rated each texture along three continua, namely, perceived roughness, hardness, and stickiness of the surfaces, shown previously as the primary dimensions of texture perception in direct touch. From the dissimilarity judgment experiment, we found that the texture percept is similar though not identical in the two scanning modes. From the adjective rating experiments, we found that while roughness ratings are similar, hardness and stickiness ratings tend to differ between scanning conditions. These differences between the two modes of scanning are apparent in perceptual space for tactile textures based on multidimensional scaling (MDS) analysis. Finally, we demonstrate that three physical quantities, vibratory power, compliance, and friction carry roughness, hardness, and stickiness information, predicting perceived dissimilarity of texture pairs with indirect touch. Given that different types of texture information are processed by separate groups of neurons across direct and indirect touch, we propose that the neural mechanisms underlying texture perception differ between scanning modes.
PMCID: PMC2635116  PMID: 17558923
Texture; multidimensional scaling; probe; dissimilarity; roughness; hardness; stickiness
4.  Genetic and systems level analysis of Drosophila sticky/citron kinase and dFmr1 mutants reveals common regulation of genetic networks 
BMC Systems Biology  2008;2:101.
In Drosophila, the genes sticky and dFmr1 have both been shown to regulate cytoskeletal dynamics and chromatin structure. These genes also genetically interact with Argonaute family microRNA regulators. Furthermore, in mammalian systems, both genes have been implicated in neuronal development. Given these genetic and functional similarities, we tested Drosophila sticky and dFmr1 for a genetic interaction and measured whole genome expression in both mutants to assess similarities in gene regulation.
We found that sticky mutations can dominantly suppress a dFmr1 gain-of-function phenotype in the developing eye, while phenotypes produced by RNAi knock-down of sticky were enhanced by dFmr1 RNAi and a dFmr1 loss-of-function mutation. We also identified a large number of transcripts that were misexpressed in both mutants suggesting that sticky and dFmr1 gene products similarly regulate gene expression. By integrating gene expression data with a protein-protein interaction network, we found that mutations in sticky and dFmr1 resulted in misexpression of common gene networks, and consequently predicted additional specific phenotypes previously not known to be associated with either gene. Further phenotypic analyses validated these predictions.
These findings establish a functional link between two previously unrelated genes. Microarray analysis indicates that sticky and dFmr1 are both required for regulation of many developmental genes in a variety of cell types. The diversity of transcripts regulated by these two genes suggests a clear cause of the pleiotropy that sticky and dFmr1 mutants display and provides many novel, testable hypotheses about the functions of these genes. As both of these genes are implicated in the development and function of the mammalian brain, these results have relevance to human health as well as to understanding more general biological processes.
PMCID: PMC2610033  PMID: 19032789
5.  Factors Involved in Tactile Texture Perception through Probes 
An understanding of texture perception by robotic systems can be developed by examining human texture perception through a probe. Like texture perception through direct touch with the finger, texture perception by indirect means of a probe is multi-dimensional, comprising rough, hard, and sticky texture continua. In this study, we describe the individual subject variability in probe-mediated texture perception, and compare similarities and differences of texture perception between direct touch and indirect touch. The results show variability among subjects, as individual subjects may choose to rely on different degrees of three texture dimensions and do so at different scanning velocities. Despite this variability between scanning conditions within each subject, the subjects make consistently reliable discriminations of textures and subjective magnitude estimates along texture continua when indirectly exploring texture surfaces with a probe. These data contribute information that is valuable to the design of robotic sensory systems, and to the understanding of sensory feedback, which is essential in teleoperations.
PMCID: PMC2711640  PMID: 19617927
sensory feedback; tactile perception; texture; probe; tool
6.  Electric nets and sticky materials for analysing oviposition behaviour of gravid malaria vectors 
Malaria Journal  2012;11:374.
Little is known about how malaria mosquitoes locate oviposition sites in nature. Such knowledge is important to help devise monitoring and control measures that could be used to target gravid females. This study set out to develop a suite of tools that can be used to study the attraction of gravid Anopheles gambiae s.s. towards visual or olfactory cues associated with aquatic habitats.
Firstly, the study developed and assessed methods for using electrocuting nets to analyse the orientation of gravid females towards an aquatic habitat. Electric nets (1m high × 0.5m wide) were powered by a 12V battery via a spark box. High and low energy settings were compared for mosquito electrocution and a collection device developed to retain electrocuted mosquitoes when falling to the ground. Secondly, a range of sticky materials and a detergent were tested to quantify if and where gravid females land to lay their eggs, by treating the edge of the ponds and the water surface. A randomized complete block design was used for all experiments with 200 mosquitoes released each day. Experiments were conducted in screened semi-field systems using insectary-reared An. gambiae s.s. Data were analysed by generalized estimating equations.
An electric net operated at the highest spark box energy of a 400 volt direct current made the net spark, creating a crackling sound, a burst of light and a burning smell. This setting caught 64% less mosquitoes than a net powered by reduced voltage output that could neither be heard nor seen (odds ratio (OR) 0.46; 95% confidence interval (CI) 0.40-0.53, p < 0.001). Three sticky boards (transparent film, glue coated black fly-screen and yellow film) were evaluated as catching devices under electric nets and the transparent and shiny black surfaces were found highly attractive (OR 41.6, 95% CI 19.8 – 87.3, p < 0.001 and OR 28.8, 95% CI 14.5 – 56.8, p < 0.001, respectively) for gravid mosquitoes to land on compared to a yellow sticky film board and therefore unsuitable as collection device under the e-nets. With a square of four e-nets around a pond combined with yellow sticky boards on average 33% (95% CI 28-38%) of mosquitoes released were collected. Sticky materials and detergent in the water worked well in collecting mosquitoes when landing on the edge of the pond or on the water surface. Over 80% of collected females were found on the water surface (mean 103, 95% CI 93–115) as compared to the edge of the artificial pond (mean 24, 95% CI 20–28).
A square of four e-nets with yellow sticky boards as a collection device can be used for quantifying the numbers of mosquitoes approaching a small oviposition site. Shiny sticky surfaces attract gravid females possibly because they are visually mistaken as aquatic habitats. These materials might be developed further as gravid traps. Anopheles gambiae s.s. primarily land on the water surface for oviposition. This behaviour can be exploited for the development of new trapping and control strategies.
PMCID: PMC3507805  PMID: 23151023
Malaria; Anopheles gambiae; Oviposition; Electric nets; Sticky film
7.  Attractiveness of employment sectors for physical therapists in Ontario, Canada (1999-2007): implication for the long term care sector 
Recruiting and retaining health professions remains a high priority for health system planners. Different employment sectors may vary in their appeal to providers. We used the concepts of inflow and stickiness to assess the relative attractiveness of sectors for physical therapists (PTs) in Ontario, Canada. Inflow was defined as the percentage of PTs working in a sector who were not there the previous year. Stickiness was defined as the transition probability that a physical therapist will remain in a given employment sector year-to-year.
A longitudinal dataset of registered PTs in Ontario (1999-2007) was created, and primary employment sector was categorized as ‘hospital’, ‘community’, ‘long term care’ (LTC) or ‘other.’ Inflow and stickiness values were then calculated for each sector, and trends were analyzed.
There were 5003 PTs in 1999, which grew to 6064 by 2007, representing a 21.2% absolute growth. Inflow grew across all sectors, but the LTC sector had the highest inflow of 32.0%. PTs practicing in hospitals had the highest stickiness, with 87.4% of those who worked in this sector remaining year-to-year. The community and other employment sectors had stickiness values of 78.2% and 86.8% respectively, while the LTC sector had the lowest stickiness of 73.4%.
Among all employment sectors, LTC had highest inflow but lowest stickiness. Given expected increases in demand for services, understanding provider transitional probabilities and employment preferences may provide a useful policy and planning tool in developing a sustainable health human resource base across all employment sectors.
PMCID: PMC3507859  PMID: 22643111
Physical therapy; Health human resources; Workforce
8.  Enhancement of Aedes albopictus collections by ovitrap and sticky adult trap 
Parasites & Vectors  2016;9:223.
In the last decades, Aedes albopictus has become an increasing public health threat in tropical as well as in more recently invaded temperate areas due to its capacity to transmit several human arboviruses, among which Dengue, Chikungunya and Zika. Enhancing the efficiency of currently used collection approaches, such as ovitraps and sticky traps, is desirable for optimal monitoring of the species abundance, for assessment of the risk of arbovirus transmission and for the optimisation of control activities.
Two sets of 4 × 4 Latin-square experiments were carried out in Tirana (Albania) to test whether modifications in ovitrap shape and size and in oviposition substrate would increase collections of Ae. albopictus eggs and whether hay-infusion would increase adult catches by sticky trap. Generalized Linear Mixed Models with negative binomial error distribution were carried out to analyse the data. Cylindrical ovitraps lined with germination paper yielded significantly higher egg catches than those exploiting either the (commonly used) wooden paddles or floating polystyrene blocks as oviposition substrates. No difference was observed between cylindrical and conical shaped ovitraps. Ovitraps and sticky traps baited with hay infusion yielded significantly higher egg and adult catches than un-baited ones. A significant relationship between ovitrap and sticky trap catches was observed both in the absence and in the presence of attractants, with ovitrap catches increasing more than sticky trap catches at increasing adult female densities.
This study provides grounds for optimisation of ovitraps and sticky traps as monitoring tools for Ae. albopictus by (i) supporting use of germination paper as most appropriate oviposition substrate; (ii) suggesting the possible use of stackable conical ovitraps for large scale monitoring; (iii) confirming the use of hay-infusion to increase egg catches in ovitraps, and showing that hay-infusion also significant increases adult catches by sticky traps.
PMCID: PMC4839143  PMID: 27102015
Mosquito monitoring; Mosquito surveillance; Aedes; Ovitrap; Sticky trap; Hay-infusion; Albania; Europe
Journal of Bacteriology  1962;83(4):860-866.
Jones, Lois M. (University of Wisconsin, Madison), C. R. McDuff, and J. B. Wilson. Phenotypic alterations in the colonial morphology of Brucella abortus due to a bacteriophage carrier state. J. Bacteriol. 83:860–866. 1962.—In the course of examining a number of Brucella cultures with a brucellaphage, it was observed that B. abortus cultures of intermediate colonial morphology, which had a blue-gray colonial appearance, were not lysed within 24 hr; in 48 hr they had developed sticky white growth in the area of the phage drop. When this growth was streaked on agar plates, both white and blue-gray colonies developed. White colonies which were sticky always carried phage and upon restreaking always gave rise to both white and blue-gray colonies. White colonies which were not sticky were rough and phage resistant. Blue-gray colonies produced only blue-gray colonies, did not carry phage, and were similar to the parent in their response to phage. When sticky white colonies were incubated for 6 hr or more in phage antiserum, all phage was eliminated and only blue-gray colonies developed. It was believed that the sticky white colonies were carrier clones in which lysis was delayed until after cell division, thus resulting in the establishment of a colony containing some phage-free progeny. With the accumulation of phage, the colony became sticky. This effect may be caused by the action of bacteriophage enzymes on the cell walls.
Brucellaphage had an extremely slow rate of adsorption on a culture of intermediate colonial morphology. A phage mutant which was more strongly lytic for cultures of intermediate colonial morphology was selected from the original phage. The adsorption rate of this phage was more rapid and the latent period shorter. A serological difference between phages could not be demonstrated.
PMCID: PMC279367  PMID: 14452300
10.  How sticky should a virus be? The impact of virus binding and release on transmission fitness using influenza as an example 
Budding viruses face a trade-off: virions need to efficiently attach to and enter uninfected cells while newly generated virions need to efficiently detach from infected cells. The right balance between attachment and detachment—the right amount of stickiness—is needed for maximum fitness. Here, we design and analyse a mathematical model to study in detail the impact of attachment and detachment rates on virus fitness. We apply our model to influenza, where stickiness is determined by a balance of the haemagglutinin (HA) and neuraminidase (NA) proteins. We investigate how drugs, the adaptive immune response and vaccines impact influenza stickiness and fitness. Our model suggests that the location in the ‘stickiness landscape’ of the virus determines how well interventions such as drugs or vaccines are expected to work. We discuss why hypothetical NA enhancer drugs might occasionally perform better than the currently available NA inhibitors in reducing virus fitness. We show that an increased antibody or T-cell-mediated immune response leads to maximum fitness at higher stickiness. We further show that antibody-based vaccines targeting mainly HA or NA, which leads to a shift in stickiness, might reduce virus fitness above what can be achieved by the direct immunological action of the vaccine. Overall, our findings provide potentially useful conceptual insights for future vaccine and drug development and can be applied to other budding viruses beyond influenza.
PMCID: PMC3899878  PMID: 24430126
influenza; within-host model; vaccines; drug treatment
11.  Biology and Trapping of Stable Flies (Diptera: Muscidae) Developing in Pineapple Residues (Ananas comosus) in Costa Rica 
Journal of Insect Science  2015;15(1):145.
Pineapple production in Costa Rica increased nearly 300-fold during the last 30 yr, and >40,000 hectares of land are currently dedicated to this crop. At the end of the pineapple cropping cycle, plants are chopped and residues incorporated into the soil in preparation for replanting. Associated with increased pineapple production has been a large increase in stable fly, Stomoxys calcitrans (L.), populations. Stable flies are attracted to, and oviposit in, the decomposing, chopped pineapple residues. In conjunction with chemical control of developing larvae, adult trapping is an important control strategy. In this study, four blue-black fabric traps, Nzi, Vavoua, Model H, and Ngu, were compared with a white sticky trap currently used for stable fly control in Costa Rica. Overall, the white sticky trap caught the highest number of stable flies, followed by the Nzi, Vavoua, Model H, and Ngu. Collections on the white sticky trap increased 16 d after residues were chopped; coinciding with the expected emergence of flies developing in the pineapple residues. During this same time period, collections in the blue-black fabric traps decreased. Sex ratio decreased from >7:1 (females:males) 3–7 d after chopping to 1:1 at 24–28 d. White sticky, Nzi and Vavoua traps collected similar numbers of colonizing flies 3–7 d after residues were chopped. However, white sticky traps collected more flies once emergence from the pineapple residues began. Although white sticky traps collected more flies than fabric traps, they remain labor intensive and environmentally unsound because of their disposable and nonbiodegradable nature.
PMCID: PMC4626667  PMID: 26454479
mass trapping; Vavoua; Nzi; Stomoxys calcitrans
12.  Short unligated sticky ends enable the observation of circularised DNA by atomic force and electron microscopies. 
Nucleic Acids Research  1998;26(9):2092-2097.
A comparative study of the stabilisation of DNA sticky ends by divalent cations was carried out by atomic force microscopy (AFM), electron microscopy and agarose gel electrophoresis. At room temperature, molecules bearing such extremities are immediately oligomerised or circularised by addition of Mg2+or Ca2+. This phenomenon, more clearly detected by AFM, requires the presence of uranyl salt, which stabilises the structures induced by Mg2+or Ca2+. DNA fragments were obtained by restriction enzymes producing sticky ends of 2 or 4 nucleotides (nt) in length with different guanine plus cytosine (GC) contents. The stability of the pairing is high when ends of 4 nt display a 100% GC-content. In that case, 95% of DNA fragments are maintained circular by the divalent cations, although 2 nt GC-sticky ends are sufficient for a stable pairing. DNA fragments with one blunt end and the other sticky appear as dimers in the presence of Mg2+. Dimerisation was analysed by varying the lengths and concentrations of DNA fragments, the base composition of the sticky ends, and also the temperature. Our observation provides a new powerful tool for construction of inverted dimers, and circularisation, ligation analysis or short bases sequence interaction studies.
PMCID: PMC147521  PMID: 9547265
MutS is a DNA repair protein that recognizes unpaired and bulged bases. When it binds to DNA it bends the double helix. We have developed a novel DNA-based nanomechanical device that measures the amount of work that a DNA-bending protein can do when it binds to the double helix. The device we report here is a scissors-like device consisting of two double-crossover (DX) molecules connected to each other by a flexible Holliday junction. The two DX components are connected by a double helix that contains the binding site for MutS; when the binding site duplex is bent, the scissors contracts. The two DX molecules are also joined by sticky ends on an edge adjacent to the binding site; the sticky ends can be disrupted if the protein binds with sufficient free energy. Those sticky ends are flanked by a pair of dyes; when the sticky ends are disrupted, the dyes separate, and the fluorescence resonance energy transfer signal can monitor the disruption. The strength of the sticky ends is readily varied, so that the ability of the protein to disrupt them can be quantitated. We use this device to measure work in conjunction with a second device that measures the bending angle resulting from protein binding, so as to calibrate the system. Our data are in good agreement with previous measurements of MutS binding, indicating that this device is able to measure the strength of binding correctly.
PMCID: PMC2848700  PMID: 20205420
DNA-Based Nanomechanical Devices; Fluorescence Resonance Energy Transfer; DNA Mispairing; DNA Repair; Unusual DNA Motifs
14.  Evaluation of a sticky trap (AedesTraP), made from disposable plastic bottles, as a monitoring tool for Aedes aegypti populations 
Parasites & Vectors  2012;5:195.
Dengue virus, which is transmitted by Aedes aegypti mosquitoes is the most important emerging viral disease, infecting more than 50 million people annually. Currently used sticky traps are useful tools for monitoring and control of A. aegypti, despite differences in efficiency, labor requirements and cost. In the present work, a field assay was carried out to evaluate the performance of a sticky trap (AedesTrap), produced using disposable material, in capturing gravid Aedes spp. females. Additionally, conditions necessary for the improved performance of the device, such as number of traps per site and location (indoors or outdoors) were evaluated.
During a one year period, traps were placed in a dengue endemic area in 28 day cycles. The trap, named AedesTrap, consisted of a disposable plastic soda bottle coated inside with colophony resin, which served as a sticky substrate. Disposable bottles were donated by restaurants, and traps were made by laboratory staff, reducing the cost of the sticky trap (less than U$3). Mosquito capture in indoor and outdoor areas was compared by placing the traps in laundry room, kitchen or bedroom (indoors) and front or back yard (outdoors). The relationship between the number of AedesTraps and quantity of captured mosquitoes was investigated by utilizing one or three traps/site.
During a 28 day cycle, a single AedesTrap was capable of capturing up to 15 A. aegypti in a house, with a mean capture of 0.5 to 2.63 females per premise. The AedesTrap collected three times more outdoors versus indoors. Similarly, the capability of detecting Aedes spp. infestation, and of capturing females, was three times higher when using three AedesTraps per house, compared with one trap per house.
AedesTrap was shown to be capable of capturing A. aegypti and other culicidae, providing information on the adult mosquito population, and allowing the identification of areas critically infested by mosquitoes. Low requirements for skilled labor together with easy maintenance and low cost are additional advantages of using this sticky trap.
PMCID: PMC3464176  PMID: 22958376
Aedes female; Sticky trap; Locality; Ovitrap; Surveillance
15.  Protein stickiness, rather than number of functional protein-protein interactions, predicts expression noise and plasticity in yeast 
BMC Systems Biology  2012;6:128.
A hub protein is one that interacts with many functional partners. The annotation of hub proteins, or more generally the protein-protein interaction “degree” of each gene, requires quality genome-wide data. Data obtained using yeast two-hybrid methods contain many false positive interactions between proteins that rarely encounter each other in living cells, and such data have fallen out of favor.
We find that protein “stickiness”, measured as network degree in ostensibly low quality yeast two-hybrid data, is a more predictive genomic metric than the number of functional protein-protein interactions, as assessed by supposedly higher quality high throughput affinity capture mass spectrometry data. In the yeast Saccharomyces cerevisiae, a protein’s high stickiness, but not its high number of functional interactions, predicts low stochastic noise in gene expression, low plasticity of gene expression across different environments, and high probability of forming a homo-oligomer. Our results are robust to a multiple regression analysis correcting for other known predictors including protein abundance, presence of a TATA box and whether a gene is essential. Once the higher stickiness of homo-oligomers is controlled for, we find that homo-oligomers have noisier and more plastic gene expression than other proteins, consistent with a role for homo-oligomerization in mediating robustness.
Our work validates use of the number of yeast two-hybrid interactions as a metric for protein stickiness. Sticky proteins exhibit low stochastic noise in gene expression, and low plasticity in expression across different environments.
PMCID: PMC3527306  PMID: 23017156
Protein-protein interaction networks; Stochastic gene expression; Evolutionary constraint; Correlomics; Cooperativity; Phenotypic plasticity
16.  Clustering of host-seeking activity of Anopheles gambiae mosquitoes at the top surface of a human-baited bed net 
Malaria Journal  2013;12:267.
Knowledge of the interactions between mosquitoes and humans, and how vector control interventions affect them, is sparse. A study exploring host-seeking behaviour at a human-occupied bed net, a key event in such interactions, is reported here.
Host-seeking female Anopheles gambiae activity was studied using a human-baited ‘sticky-net’ (a bed net without insecticide, coated with non-setting adhesive) to trap mosquitoes. The numbers and distribution of mosquitoes captured on each surface of the bed net were recorded and analysed using non-parametric statistical methods and random effects regression analysis. To confirm sticky-net reliability, the experiment was repeated using a pitched sticky-net (tilted sides converging at apex, i.e., neither horizontal nor vertical). The capture efficiency of horizontal and vertical sticky surfaces were compared, and the potential repellency of the adhesive was investigated.
In a semi-field experiment, more mosquitoes were caught on the top (74-87%) than on the sides of the net (p < 0.001). In laboratory experiments, more mosquitoes were caught on the top than on the sides in human-baited tests (p < 0.001), significantly different to unbaited controls (p < 0.001) where most mosquitoes were on the sides (p = 0.047). In both experiments, approximately 70% of mosquitoes captured on the top surface were clustered within a 90 × 90 cm (or lesser) area directly above the head and chest (p < 0.001). In pitched net tests, similar clustering occurred over the sleeper’s head and chest in baited tests only (p < 0.001). Capture rates at horizontal and vertical surfaces were not significantly different and the sticky-net was not repellent.
This study demonstrated that An. gambiae activity occurs predominantly within a limited area of the top surface of bed nets. The results provide support for the two-in-one bed net design for managing pyrethroid-resistant vector populations. Further exploration of vector behaviour at the bed net interface could contribute to additional improvements in insecticide-treated bed net design or the development of novel vector control tools.
PMCID: PMC3733746  PMID: 23902661
Bed net; LLIN; ITN; Anopheles gambiae; Two-in-one; Vector behaviour; Mosquito; Malaria; Pyrethroid; Insecticide resistance
17.  Local acting Sticky-trap inhibits vascular endothelial growth factor dependent pathological angiogenesis in the eye 
EMBO Molecular Medicine  2014;6(5):604-623.
Current therapeutic antiangiogenic biologics used for the treatment of pathological ocular angiogenesis could have serious side effects due to their interference with normal blood vessel physiology. Here, we report the generation of novel antivascular endothelial growth factor-A (VEGF) biologics, termed VEGF “Sticky-traps,” with unique properties that allow for local inhibition of angiogenesis without detectable systemic side effects. Using genetic and pharmacological approaches, we demonstrated that Sticky-traps could locally inhibit angiogenesis to at least the same extent as the original VEGF-trap that also gains whole-body access. Sticky-traps did not cause systemic effects, as shown by uncompromised wound healing and normal tracheal vessel density. Moreover, if injected intravitreally, recombinant Sticky-trap remained localized to various regions of the eye, such as the inner-limiting membrane and ciliary body, for prolonged time periods, without gaining access either to the photoreceptors/choriocapillaris area or the circulation. These unique pharmacological characteristics of Sticky-trap could allow for safe treatment of pathological angiogenesis in patients with diabetic retinopathy and retinopathy of pre-maturity.
PMCID: PMC4023884  PMID: 24705878
angiogenesis; diabetic retinopathy; retinopathy of prematurity; Sticky-trap; VEGF
18.  Association of Clinical and Radiographic Features with Perinephric “Sticky” Fat 
Journal of Endourology  2013;27(3):370-373.
Background and Purpose
The discovery of thick, adherent, perinephric sticky fat (PSF) is relatively common during open or laparoscopic retroperitoneal surgery. To our knowledge, however, there has been no previous analysis of clinical or radiographic features associated with the development of PSF or of perioperative outcomes for those patients in whom it is found. Our objective is to analyze potential predictive features and determine whether there is any effect on clinical or pathologic outcomes for patients with perinephric sticky fat.
Patients and Methods
Patients undergoing partial nephrectomy or laparoscopic cryoablation with available preoperative imaging were identified from 2005 to 2011. Operative records were reviewed to identify patients with and without PSF. Preoperative images and medical records were examined to obtain patient data regarding potential predictors as well as clinical and pathologic outcomes.
A total of 29 patients were identified—16 with PSF and 13 controls. Statistically significant factors associated with PSF included sex, tumor size, presence of perinephric stranding, tumor >50% exophytic, and thickness of perinephric fat (P<0.05). Median total operative time for patients with sticky fat was nearly 40 minutes longer than the control group (228 min vs 190 min, P<0.05). All four (17%) patients with Fuhrman grade 3 or 4 renal-cell carcinoma were from the sticky fat group (P=0.09).
Despite the small sample size, multiple possible factors associated with perinephric sticky fat were identified and may provide guidance for future investigation of this phenomenon.
PMCID: PMC4277038  PMID: 22966767
19.  Species composition of phlebotomine sand flies and bionomics of Phlebotomus orientalis (Diptera: Psychodidae) in an endemic focus of visceral leishmaniasis in Tahtay Adiyabo district, Northern Ethiopia 
Parasites & Vectors  2015;8:248.
Visceral leishmaniasis (VL) is a neglected tropical disease, which is strongly associated with poverty. VL caused by Leishmania donovani and transmitted by Phlebotomus orientalis is endemic in various remote areas of north and north-west Ethiopia. The present study was designed to determine the sand fly fauna and bionomics of P. orientalis in the VL endemic focus of Tahtay Adiyabo district.
Sand flies were collected using CDC light traps (n = 602), sticky traps (n = 9,350) and indoor pyrethrum spray catches (n = 578 house visits) from indoor, peri-domestic and agricultural field habitats between May 2011 to April 2012. All sand fly specimens collected were identified to species level and counted.
In total, 100,772 sand fly specimens, belonging to 25 sand fly species (nine Phlebotomus and sixteen Sergentomyia) were collected and identified. S. africana and P. orientalis made up 59.1% and 23.5% of the collected sand flies, respectively. As it could be determined from the proportion of collections from outdoor (peri-domestic and agricultural fields) and indoor locations, P. orientalis appears to exhibit increased exophilic behavior. The outdoor to indoor index was 79:1 on m2 of sticky traps. Mean density of P. orientalis caught was significantly higher on horizontally placed sticky traps (mean = 60 ± 14.56/m2/night) than vertically deployed sticky traps (12 ± 3.57/m2/night). The highest abundance of P. orientalis occurred between March and April. Through July to September, there was a sharp decline in abundance of P. orientalis population. Regarding climatic variables, P. orientalis density in light traps and on sticky traps showed a significant positive and negative association with temperature and relative humidity, respectively. However, non-significant negative correlation was observed with rainfall pattern.
Overall, P. orientalis was found to be the most abundant Phlebotomus species, showing marked seasonal abundance that mainly peaks during the dry season (March to April). Likewise, the people in the area usually sleep in compounds during these months that potentially expose them to a high risk of peri-domestic VL transmission.
PMCID: PMC4438477  PMID: 25907252
Bionomics; Population dynamics; Phlebotomus orientalis; Sand fly fauna; Tahtay Adiyabo; Visceral leishmaniasis
20.  Mineral nutrient uptake from prey and glandular phosphatase activity as a dual test of carnivory in semi-desert plants with glandular leaves suspected of carnivory 
Annals of Botany  2009;104(4):649-654.
Background and Aims
Ibicella lutea and Proboscidea parviflora are two American semi-desert species of glandular sticky plants that are suspected of carnivory as they can catch small insects. The same characteristics might also hold for two semi-desert plants with glandular sticky leaves from Israel, namely Cleome droserifolia and Hyoscyamus desertorum. The presence of proteases on foliar hairs, either secreted by the plant or commensals, detected using a simple test, has long been considered proof of carnivory. However, this test does not prove whether nutrients are really absorbed from insects by the plant. To determine the extent to which these four species are potentially carnivorous, hair secretion of phosphatases and uptake of N, P, K and Mg from fruit flies as model prey were studied in these species and in Roridula gorgonias and Drosophyllum lusitanicum for comparison. All species examined possess morphological and anatomical adaptations (hairs or emergences secreting sticky substances) to catch and kill small insects.
The presence of phosphatases on foliar hairs was tested using the enzyme-labelled fluorescence method. Dead fruit flies were applied to glandular sticky leaves of experimental plants and, after 10–15 d, mineral nutrient content in their spent carcasses was compared with initial values in intact flies after mineralization.
Key Results
Phosphatase activity was totally absent on Hyoscyamus foliar hairs, a certain level of activity was usually found in Ibicella, Proboscidea and Cleome, and a strong response was found in Drosophyllum. Roridula exhibited only epidermal activity. However, only Roridula and Drosophyllum took up nutrients (N, P, K and Mg) from applied fruit flies.
Digestion of prey and absorption of their nutrients are the major features of carnivory in plants. Accordingly, Roridula and Drosophyllum appeared to be fully carnivorous; by contrast, all other species examined are non-carnivorous as they did not meet the above criteria.
PMCID: PMC2729641  PMID: 19556266
Roridula gorgonias; Drosophyllum lusitanicum; Proboscidea parviflora; Ibicella lutea; Cleome droserifolia; Hyoscyamus desertorum; phosphatase; phosphomonoesters; fruit flies; N, P, K, Mg uptake from prey
21.  Identification of Fluorescent Compounds with Non-Specific Binding Property via High Throughput Live Cell Microscopy 
PLoS ONE  2012;7(1):e28802.
Compounds exhibiting low non-specific intracellular binding or non-stickiness are concomitant with rapid clearing and in high demand for live-cell imaging assays because they allow for intracellular receptor localization with a high signal/noise ratio. The non-stickiness property is particularly important for imaging intracellular receptors due to the equilibria involved.
Three mammalian cell lines with diverse genetic backgrounds were used to screen a combinatorial fluorescence library via high throughput live cell microscopy for potential ligands with high in- and out-flux properties. The binding properties of ligands identified from the first screen were subsequently validated on plant root hair. A correlative analysis was then performed between each ligand and its corresponding physiochemical and structural properties.
The non-stickiness property of each ligand was quantified as a function of the temporal uptake and retention on a cell-by-cell basis. Our data shows that (i) mammalian systems can serve as a pre-screening tool for complex plant species that are not amenable to high-throughput imaging; (ii) retention and spatial localization of chemical compounds vary within and between each cell line; and (iii) the structural similarities of compounds can infer their non-specific binding properties.
We have validated a protocol for identifying chemical compounds with non-specific binding properties that is testable across diverse species. Further analysis reveals an overlap between the non-stickiness property and the structural similarity of compounds. The net result is a more robust screening assay for identifying desirable ligands that can be used to monitor intracellular localization. Several new applications of the screening protocol and results are also presented.
PMCID: PMC3252290  PMID: 22242152
22.  Estrogen formulations and beauty care practices in Japanese women 
Traditionally, oral estrogens have been used for hormone replacement therapy. However, in Japan, additional estrogen formulations have been used, including transdermal patches and transdermal gels. The latter have a unique commonality with cosmetics because both of them are applied to the skin. Beauty care is one of the most important lifestyle factors for women, and it has been reported that the amount of attention paid to beauty care has an effect in determining whether or not women will choose to undergo HRT during menopause. Therefore, our study focused on estrogen formulations and beauty care practices.
Patients and methods
Fifty women who use hormone replacement therapy were recruited from the outpatient clinic of Tohoku University Hospital. They were treated with oral conjugated estrogen (n = 11), transdermal 17β-estradiol patch (n = 11), and transdermal 17β-estradiol gel (n = 28). They completed a questionnaire to assess their lifestyle (beauty care practices and exercise habits) and their compliance. The transdermal gel users were further interviewed about their subjective impressions regarding “smell”, “sticky feeling”, “spreadability”, and “irritation” on the skin using a five-grade scale.
There were no differences in the usability of medicines and patient compliance among the estrogen formulations. We observed a positive tendency between the level of beauty care and transdermal gel use (P = 0.0645, ordinary logistic regression analysis). The gel users placed top priority on a lack of “sticky feeling” but the subjective impression regarding “sticky feeling” was worst among the four factors (P < 0.01, Steel–Dwass test). Correspondence analysis showed that the subjective impressions of transdermal gel corresponding to usability in the range of “moderate” to “very good” and “sticky feeling” greatly affected the usability of the formulation.
These results suggest that the level of attention to beauty care plays some role in the choice of estrogen formulations.
PMCID: PMC3271811  PMID: 22312196
HRT; estrogen; transdermal gel; cosmetics; subjective impression
23.  The Effects of Mindfulness-Based Cognitive Therapy on Affective Memory Recall Dynamics in Depression: A Mechanistic Model of Rumination 
Objectives: converging research suggests that mindfulness training exerts its therapeutic effects on depression by reducing rumination. Theoretically, rumination is a multifaceted construct that aggregates multiple neurocognitive aspects of depression, including poor executive control, negative and overgeneral memory bias, and persistence or stickiness of negative mind states. Current measures of rumination, most-often self-reports, do not capture these different aspects of ruminative tendencies, and therefore are limited in providing detailed information about the mechanisms of mindfulness. Methods: we developed new insight into the potential mechanisms of rumination, based on three model-based metrics of free recall dynamics. These three measures reflect the patterns of memory retrieval of valenced information: the probability of first recall (Pstart) which represents initial affective bias, the probability of staying with the same valence category rather than switching, which indicates strength of positive or negative association networks (Pstay), and probability of stopping (Pstop) or ending recall within a given valence, which indicates persistence or stickiness of a mind state. We investigated the effects of Mindfulness-Based Cognitive Therapy (MBCT; N = 29) vs. wait-list control (N = 23) on these recall dynamics in a randomized controlled trial in individuals with recurrent depression. Participants completed a standard laboratory stressor, the Trier Social Stress Test, to induce negative mood and activate ruminative tendencies. Following that, participants completed a free recall task consisting of three word lists. This assessment was conducted both before and after treatment or wait-list. Results: while MBCT participant’s Pstart remained relatively stable, controls showed multiple indications of depression-related deterioration toward more negative and less positive bias. Following the intervention, MBCT participants decreased in their tendency to sustain trains of negative words and increased their tendency to sustain trains of positive words. Conversely, controls showed the opposite tendency: controls stayed in trains of negative words for longer, and stayed in trains of positive words for less time relative to pre-intervention scores. MBCT participants tended to stop recall less often with negative words, which indicates less persistence or stickiness of negatively valenced mental context. Conclusion: MBCT participants showed a decrease in patterns that may perpetuate rumination on all three types of recall dynamics (Pstart, Pstay, and Pstop), compared to controls. MBCT may weaken the strength of self-perpetuating negative associations networks that are responsible for the persistent and “sticky” negative mind states observed in depression, and increase the positive associations that are lacking in depression. This study also offers a novel, objective method of measuring several indices of ruminative tendencies indicative of the underlying mechanisms of rumination.
PMCID: PMC3446543  PMID: 23049507
memory; emotional processing; mindfulness; free recall
24.  Are Yellow Sticky Traps an Effective Method for Control of Sweetpotato Whitefly, Bemisia tabaci, in the Greenhouse or Field? 
Yellow sticky traps are a common method for monitoring many pests, but it has not been shown whether they could be used as a control method. In this study the impact of yellow sticky traps on the population dynamics of the sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) was determined in the greenhouse and field. In the greenhouse, yellow sticky traps significantly suppressed the population increase of adult and immature whiteflies. The whitefly densities in the greenhouse with traps were significantly lower than the greenhouse without traps. In the field, traps did not have a significant impact on the population dynamics of adult and immature whiteflies. The densities in fields with traps were very similar to fields without traps. These results suggest that yellow sticky traps can be used as an effective method for the control of whiteflies in the greenhouse, but not in the field. This information will prove useful for the effective management of whiteflies in greenhouses.
PMCID: PMC3620036  PMID: 23445077
entire crop growth period; population dynamics
25.  Evaluation of the influence of electric nets on the behaviour of oviposition site seeking Anopheles gambiae s.s 
Parasites & Vectors  2014;7:272.
Electric nets (e-nets) are used to analyse the flight behaviour of insects and have been used extensively to study the host-oriented flight of tsetse flies. Recently we adapted this tool to analyse the oviposition behaviour of gravid malaria vectors, Anopheles gambiae s.s., orienting towards aquatic habitats and traps by surrounding an artificial pond with e-nets and collecting electrocuted mosquitoes on sticky boards on the ground next to the nets. Here we study whether e-nets themselves affect the responses of gravid An. gambiae s.s..
Dual-choice experiments were carried out in 80 m2 screened semi-field systems where 200 gravid An. gambiae s.s. were released each night for 12 nights per experiment. The numbers of mosquito landing on or approaching an oviposition site were studied by adding detergent to the water in an artificial pond or surrounding the pond with a square of e-nets. We also assessed whether the supporting framework of the nets or the sticky boards used to retain electrocuted mosquitoes influenced the catch.
Two similar detergent treated ponds presented in choice tests caught an equal proportion of the mosquitoes released, whereas a pond surrounded by e-nets caught a higher proportion than an open pond (odds ratio (OR) 1.7, 95% confidence interval (CI) 1.1 - 2.7; p < 0.017). The separate evaluation of the impact of the square of electric nets and the yellow boards on the approach of gravid females towards a pond suggests that the tower-like construction of the square of electric nets did not restrict the approach of females but the yellow sticky boards on the ground attract gravid females to a source of water (OR 2.7 95% CI 1.7 – 4.3; p < 0.001).
The trapping efficiency of the electric nets is increased when large yellow sticky boards are placed on the ground next to the e-nets to collect electrocuted mosquitoes, possibly because of increased visual contrast to the aquatic habitat. It is therefore important when comparing two treatments that the same trapping device is used in both. The importance of contrast around artificial habitats might be exploited to improve collections of An. gambiae s.s. in gravid traps.
PMCID: PMC4067519  PMID: 24948354
Electric net; Oviposition behaviour; Aquatic habitat; Anopheles gambiae; Sticky trap; Gravid trap

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