407 research outputs found
Tin whisker mitigation by means of a postelectroplating electrochemical oxidation treatment
There are very few studies that have investigated directly the effect of an oxide film on tin whisker growth, since the ‘cracked oxide theory’ was proposed by Tu in 19941. The current study has investigated the effect of an electrochemically produced oxide on tin whisker growth, for both Sn-Cu electrodeposits on Cu and pure Sn electrodeposits on brass. X-ray photoelectron spectroscopy (XPS) has been used to investigate the effect of the applied electrochemical oxidation potential on the oxide film thickness. Focused ion beam (FIB) has been used to prepare cross sections from electrodeposited samples to investigate the influence of the electrochemically formed oxide film on deposit microstructure during long-term room temperature storage. The XPS studies show that the thickness of electrochemically formed oxide film is directly influenced by the applied potential and the total charge passed. Whisker growth studies show that the electrochemical oxidation treatment mitigates whisker growth for both Sn-Cu electrodeposits on Cu and pure Sn electrodeposits on brass. For Sn electrodeposits on brass, the electrochemically formed oxide greatly reduces both the formation of zinc oxide at the surface and the formation of intermetallic compounds, which results in the mitigation of tin whisker growth. For Sn-Cu electrodeposits on Cu, the electrochemically formed oxide has no apparent effect on intermetallic compound formation and acts simply as a physical barrier to hinder tin whisker growth
Ablation of rat TRPV1-expressing Adelta/C-fibers with resiniferatoxin: analysis of withdrawal behaviors, recovery of function and molecular correlates
<p>Abstract</p> <p>Background</p> <p>Ablation of TRPV1-expressing nociceptive fibers with the potent capsaicin analog resiniferatoxin (RTX) results in long lasting pain relief. RTX is particularly adaptable to focal application, and the induced chemical axonopathy leads to analgesia with a duration that is influenced by dose, route of administration, and the rate of fiber regeneration. TRPV1 is expressed in a subpopulation of unmyelinated C- and lightly myelinated Adelta fibers that detect changes in skin temperature at low and high rates of noxious heating, respectively. Here we investigate fiber-type specific behaviors, their time course of recovery and molecular correlates of axon damage and nociception using infrared laser stimuli following an RTX-induced peripheral axonopathy.</p> <p>Results</p> <p>RTX was injected into rat hind paws (mid-plantar) to produce thermal hypoalgesia. An infrared diode laser was used to stimulate Adelta fibers in the paw with a small-diameter (1.6 mm), high-energy, 100 msec pulse, or C-fibers with a wide-diameter (5 mm), long-duration, low-energy pulse. We monitored behavioral responses to indicate loss and regeneration of fibers. At the site of injection, responses to C-fiber stimuli were significantly attenuated for two weeks after 5 or 50 ng RTX. Responses to Adelta stimuli were significantly attenuated for two weeks at the highest intensity stimulus, and for 5 weeks to a less intense Adelta stimulus. Stimulation on the toe, a site distal to the injection, showed significant attenuation of Adelta responses for 7- 8 weeks after 5 ng, or 9-10 weeks after 50 ng RTX. In contrast, responses to C-fiber stimuli exhibited basically normal responses at 5 weeks after RTX. During the period of fiber loss and recovery, molecular markers for nerve regeneration (ATF3 and galanin) are upregulated in the dorsal root ganglia (DRG) when behavior is maximally attenuated, but markers of nociceptive activity (c-Fos in spinal cord and MCP-1 in DRG), although induced immediately after RTX treatment, returned to normal.</p> <p>Conclusion</p> <p>Behavioral recovery following peripheral RTX treatment is linked to regeneration of TRPV1-expressing Adelta and C-fibers and sustained expression of molecular markers. Infrared laser stimulation is a potentially valuable tool for evaluating the behavioral role of Adelta fibers in pain and pain control.</p
The E6E7 oncoproteins of cutaneous human papillomavirus type 38 interfere with the interferon pathway
Non-melanoma skin cancer is the most frequent malignancy in Caucasian populations. Evidence suggests the involvement of cutaneous Human Papillomavirus (HPV) of the genus beta () in this disease. The ability of E6 and E7 of mucosal HPV to promote cellular transformation and inhibit immune response-related pathways plays a key role in cervical carcinogenesis. HPV-38 E6 and E7 display transforming activities in in vitro and in vivo models, but their impact on immune surveillance is unknown. Here we show that HPV-38 E6 and E7 affect the IFN-induced up-regulation of MHC class I. Expression of the two viral proteins in HaCaT keratinocytes led to a decrease of MHC I levels. This down-regulation is associated with a reduction of expression of MHC I heavy chain, of the peptide chaperone TAP and of the STAT-1 downstream effector IRF-1. The down-regulation of these proteins is ultimately due to the inhibition of STAT-1 expression. Analysis of cells expressing either HPV-38 E6 or E7 suggests that these effects are primarily the result of E6 expression, although a contribution by E7 cannot be excluded. We conclude that HPV-38 encodes oncoproteins that potentially contribute to the evasion of host immune surveillance
The Undergraduate Training in Genomics (UTRIG) Initiative: Early & Active Training for Physicians in the Genomic Medicine Era
Genomic medicine is transforming patient care. However, the speed of development has left a knowledge gap between discovery and effective implementation into clinical practice. Since 2010, the Training Residents in Genomics (TRIG) Working Group has found success in building a rigorous genomics curriculum with implementation tools aimed at pathology residents in postgraduate training years 1-4. Based on the TRIG model, the interprofessional Undergraduate Training in Genomics (UTRIG) Working Group was formed. Under the aegis of the Undergraduate Medical Educators Section of the Association of Pathology Chairs and representation from nine additional professional societies, UTRIG\u27s collaborative goal is building medical student genomic literacy through development of a ready-to-use genomics curriculum. Key elements to the UTRIG curriculum are expert consensus-driven objectives, active learning methods, rigorous assessment and integration
Designing succinct structural alphabets
Motivation: The 3D structure of a protein sequence can be assembled from the substructures corresponding to small segments of this sequence. For each small sequence segment, there are only a few more likely substructures. We call them the ‘structural alphabet’ for this segment. Classical approaches such as ROSETTA used sequence profile and secondary structure information, to predict structural fragments. In contrast, we utilize more structural information, such as solvent accessibility and contact capacity, for finding structural fragments
Learning probabilistic models of hydrogen bond stability from molecular dynamics simulation trajectories
Hydrogen bonds (H-bonds) play a key role in both the formation and stabilization of protein structures. H-bonds involving atoms from residues that are close to each other in the main-chain sequence stabilize secondary structure elements. H-bonds between atoms from distant residues stabilize a protein’s tertiary structure. However, H-bonds greatly vary in stability. They form and break while a protein deforms. For instance, the transition of a protein from a nonfunctional to a functional state may require some H-bonds to break and others to form. The intrinsic strength of an individual H-bond has been studied from an energetic viewpoint, but energy alone may not be a very good predictor. Other local interactions may reinforce (or weaken) an H-bond. This paper describes inductive learning methods to train a protein-independent probabilistic model of H-bond stability from molecular dynamics (MD) simulation trajectories. The training data describes H-bond occurrences at successive times along these trajectories by the values of attributes called predictors. A trained model is constructed in the form of a regression tree in which each non-leaf node is a Boolean test (split) on a predictor. Each occurrence of an H-bond maps to a path in this tree from the root to a leaf node. Its predicted stability is associated with the leaf node. Experimental results demonstrate that such models can predict H-bond stability quite well. In particular, their performance is roughly 20 % better than that of models based on H-bond energy alone. In addition, they can accurately identify a large fraction of the least stable H-bonds in a give
A Wasp Manipulates Neuronal Activity in the Sub-Esophageal Ganglion to Decrease the Drive for Walking in Its Cockroach Prey
BACKGROUND: The parasitoid Jewel Wasp hunts cockroaches to serve as a live food supply for its offspring. The wasp stings the cockroach in the head and delivers a cocktail of neurotoxins directly inside the prey's cerebral ganglia. Although not paralyzed, the stung cockroach becomes a living yet docile 'zombie', incapable of self-initiating spontaneous or evoked walking. We show here that such neuro-chemical manipulation can be attributed to decreased neuronal activity in a small region of the cockroach cerebral nervous system, the sub-esophageal ganglion (SEG). A decrease in descending permissive inputs from this ganglion to thoracic central pattern generators decreases the propensity for walking-related behaviors. METHODOLOGY AND PRINCIPAL FINDINGS: We have used behavioral, neuro-pharmacological and electrophysiological methods to show that: (1) Surgically removing the cockroach SEG prior to wasp stinging prolongs the duration of the sting 5-fold, suggesting that the wasp actively targets the SEG during the stinging sequence; (2) injecting a sodium channel blocker, procaine, into the SEG of non-stung cockroaches reversibly decreases spontaneous and evoked walking, suggesting that the SEG plays an important role in the up-regulation of locomotion; (3) artificial focal injection of crude milked venom into the SEG of non-stung cockroaches decreases spontaneous and evoked walking, as seen with naturally-stung cockroaches; and (4) spontaneous and evoked neuronal spiking activity in the SEG, recorded with an extracellular bipolar microelectrode, is markedly decreased in stung cockroaches versus non-stung controls. CONCLUSIONS AND SIGNIFICANCE: We have identified the neuronal substrate responsible for the venom-induced manipulation of the cockroach's drive for walking. Our data strongly support previous findings suggesting a critical and permissive role for the SEG in the regulation of locomotion in insects. By injecting a venom cocktail directly into the SEG, the parasitoid Jewel Wasp selectively manipulates the cockroach's motivation to initiate walking without interfering with other non-related behaviors
Exploitation of Other Social Amoebae by Dictyostelium caveatum
Dictyostelium amoebae faced with starvation trigger a developmental program during which many cells aggregate and form fruiting bodies that consist of a ball of spores held aloft by a thin stalk. This developmental strategy is open to several forms of exploitation, including the remarkable case of Dictyostelium caveatum, which, even when it constitutes 1/10(3) of the cells in an aggregate, can inhibit the development of the host and eventually devour it. We show that it accomplishes this feat by inhibiting a region of cells, called the tip, which organizes the development of the aggregate into a fruiting body. We use live-cell microscopy to define the D. caveatum developmental cycle and to show that D. caveatum amoebae have the capacity to ingest amoebae of other Dictyostelid species, but do not attack each other. The block in development induced by D. caveatum does not affect the expression of specific markers of prespore cell or prestalk cell differentiation, but does stop the coordinated cell movement leading to tip formation. The inhibition mechanism involves the constitutive secretion of a small molecule by D. caveatum and is reversible. Four Dictyostelid species were inhibited in their development, while D. caveatum is not inhibited by its own compound(s). D. caveatum has evolved a predation strategy to exploit other members of its genus, including mechanisms of developmental inhibition and specific phagocytosis
Human-cat relationship in an oceanic biosphere reserve: the case of La Palma Island, Canary archipelago
Removal of feral cats from island environments is a useful mechanism by which their ecological impact on endangered species can be reduced or ended. Nevertheless, because cats are anthropogenic in their origins, social perceptions of management practices play a large role in their implementation. Four-hundred questionnaires were delivered (386 were returned) with 100 going to each of the following: local residents; environmental workers; tourists; and, hunters. Questions explored respondents’ knowledge about island biodiversity and invasive species as well as attitudes towards cat population management methods. Habitat destruction and introduction of invasive species were considered the main threats for the conservation of island biodiversity. Most respondents considered cats to have a negative impact on biodiversity and sterilization campaigns were considered most appropriate for cat population control. Several free sterilization campaigns have been conducted in La Palma Island Biosphere Reserve in order to reduce free-ranging cats and were well received by local people. This research, which combined concepts of management, ecology and social sciences, provides valuable insights which may to be applicable on several other islands where cats and people are present and in conflict with conservation priorities
An Image-Free Opto-Mechanical System for Creating Virtual Environments and Imaging Neuronal Activity in Freely Moving Caenorhabditis elegans
Non-invasive recording in untethered animals is arguably the ultimate step in the analysis of neuronal function, but such recordings remain elusive. To address this problem, we devised a system that tracks neuron-sized fluorescent targets in real time. The system can be used to create virtual environments by optogenetic activation of sensory neurons, or to image activity in identified neurons at high magnification. By recording activity in neurons of freely moving C. elegans, we tested the long-standing hypothesis that forward and reverse locomotion are generated by distinct neuronal circuits. Surprisingly, we found motor neurons that are active during both types of locomotion, suggesting a new model of locomotion control in C. elegans. These results emphasize the importance of recording neuronal activity in freely moving animals and significantly expand the potential of imaging techniques by providing a mean to stabilize fluorescent targets
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