300 research outputs found
Circadian immunity from bench to bedside: A practical guide
The immune system is built to counteract unpredictable threats, yet it relies on predictable cycles of activity to function properly. Daily rhythms in immune function are an expanding area of study, and many originate from a genetically based timekeeping mechanism known as the circadian clock. The challenge is how to harness these biological rhythms to improve medical interventions. Here, we review recent literature documenting how circadian clocks organize fundamental innate and adaptive immune activities, the immunologic consequences of circadian rhythm and sleep disruption, and persisting knowledge gaps in the field. We then consider the evidence linking circadian rhythms to vaccination, an important clinical realization of immune function. Finally, we discuss practical steps to translate circadian immunity to the patient\u27s bedside
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
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
Characterization of four cell lines persistently infected with measles virus
Persistently infected cell lines were established by infecting Vero cells with four different strains of measles virus: Edmonston “wild type”, Schwarz vaccine strain passaged at high multiplicity of infection, Hallé SSPE strain, and a temperature sensitive mutant of Edmonston strain, designated ts 841. The four cell lines have continued to produce virus at a constant low level over a period of more than two years, although cytopathology and hemagglutinating ability have varied with cell passage. Only virus from cells originally infected with ts 841 appears to be temperature sensitive. In each of the cell lines a sizable population of low density, interfering virus particles was generated, indicating that this is an important mechanism for these four cell lines in maintenance of the measles virus persistent infection.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41690/1/705_2005_Article_BF01314863.pd
Evaluation of 2-deoxy-D-glucose as a chemotherapeutic agent: mechanism of cell death
Nutrient deprivation has been shown to cause cancer cell death. To exploit nutrient deprivation as anti-cancer therapy, we investigated the effects of the anti-metabolite 2-deoxy-D-glucose on breast cancer cells in vitro. This compound has been shown to inhibit glucose metabolism. Treatment of human breast cancer cell lines with 2-deoxy-D-glucose results in cessation of cell growth in a dose dependent manner. Cell viability as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide conversion assay and clonogenic survival are decreased with 2-deoxy-D-glucose treatment indicating that 2-deoxy-D-glucose causes breast cancer cell death. The cell death induced by 2-deoxy-D-glucose was found to be due to apoptosis as demonstrated by induction of caspase 3 activity and cleavage of poly (ADP-ribose) polymerase. Breast cancer cells treated with 2-deoxy-D-glucose express higher levels of Glut1 transporter protein as measured by Western blot analysis and have increased glucose uptake compared to non-treated breast cancer cells. From these results we conclude that 2-deoxy-D-glucose treatment causes death in human breast cancer cell lines by the activation of the apoptotic pathway. Our data suggest that breast cancer cells treated with 2-deoxy-D-glucose accelerate their own demise by initially expressing high levels of glucose transporter protein, which allows increased uptake of 2-deoxy-D-glucose, and subsequent induction of cell death. These data support the targeting of glucose metabolism as a site for chemotherapeutic intervention by agents such as 2-deoxy-D-glucose
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
Formation and Growth of Oligomers: A Monte Carlo Study of an Amyloid Tau Fragment
Small oligomers formed early in the process of amyloid fibril formation may be the major toxic species in Alzheimer's disease. We investigate the early stages of amyloid aggregation for the tau fragment AcPHF6 (Ac-VQIVYK-NH2) using an implicit solvent all-atom model and extensive Monte Carlo simulations of 12, 24, and 36 chains. A variety of small metastable aggregates form and dissolve until an aggregate of a critical size and conformation arises. However, the stable oligomers, which are β-sheet-rich and feature many hydrophobic contacts, are not always growth-ready. The simulations indicate instead that these supercritical oligomers spend a lengthy period in equilibrium in which considerable reorganization takes place accompanied by exchange of chains with the solution. Growth competence of the stable oligomers correlates with the alignment of the strands in the β-sheets. The larger aggregates seen in our simulations are all composed of two twisted β-sheets, packed against each other with hydrophobic side chains at the sheet–sheet interface. These β-sandwiches show similarities with the proposed steric zipper structure for PHF6 fibrils but have a mixed parallel/antiparallel β-strand organization as opposed to the parallel organization found in experiments on fibrils. Interestingly, we find that the fraction of parallel β-sheet structure increases with aggregate size. We speculate that the reorganization of the β-sheets into parallel ones is an important rate-limiting step in the formation of PHF6 fibrils
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