The Clinicians\u27 Guide to Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob disease, a transmissible, rapidly progressive dementia of unknown etiology, mimics Alzheimer\u27s disease, presents in middle life, and affects many central nervous system structures. The disease progresses in three distinct stages, culminating in death. Its occurrence is sporadic and its distribution worldwide. Pathological changes are varied, but spongy degeneration of the neuropil is classic. Research on scrapie, the animal model of Creutzfeldt-Jakob disease, has demonstrated that this unconventional, slow disease is transmitted via a small (less than 50,000 mW) particle, which is composed principally of protein. How this infectious particle, variably named prion, virino, or slow virus, invokes disease or is transmitted is unclear. The agent does not evoke a host immune response, nor does it appear to contain nucleic acid. No treatment has proven successful, although amantadine has been partially effective in some cases. Decreased brain concentrations of dopamine and norepinephrine are associated pharmacological abnormalities

A prelysosomal compartment sequesters membrane-impermeant fluorescent dyes from the cytoplasmic matrix of J774 macrophages

After the membrane impermeant dye Lucifer Yellow is introduced into the cytoplasmic matrix of J774 cells, the dye is sequestered within cytoplasmic vacuoles and secreted into the extracellular medium. In the present work we studied the intracellular transport of Lucifer Yellow in J774 macrophages and the nature of the cytoplasmic vacuoles into which this dye is sequestered. When the lysosomal system of J774 cells was prelabeled with a Texas red ovalbumin conjugate and Lucifer Yellow was then loaded into the cytoplasm of the cells by ATP-mediated permeabilization of the plasma membrane, the vacuoles that sequestered Lucifer Yellow 30 min later were distinct from the Texas red-stained lysosomes. After an additional 30 min Lucifer Yellow and Texas red colocalized in the same membrane bound compartments, indicating that the Lucifer Yellow had been delivered to lysosomes. We next prelabeled the plasma membrane of J774 cells with anti-macrophage antibody and Texas red protein A before Lucifer Yellow was loaded into the cells. The phase-lucent vacuoles that subsequently sequestered Lucifer Yellow also stained with Texas red, showing that they were part of the endocytic pathway. J774 cells were fractionated on percoll density gradients either 15 or 60 min after Lucifer Yellow was introduced into the cytoplasmic matrix of the cells. In cells fractionated after 15 min, Lucifer Yellow was contained within the fractions of light buoyant density that contain plasma membrane and endosomes; the dye later appeared in vesicles of higher density which contained lysosomes. Secretion of Lucifer Yellow from the cytoplasmic matrix of J774 cells is inhibited by the organic anion transport blocker probenecid. We found that probenecid also reversibly inhibited sequestration of dye, indicating that sequestration of dye within cytoplasmic vacuoles was also mediated by organic anion transporters. These studies show that the vacuoles that sequester Lucifer Yellow from the cytoplasmic matrix of J774 cells possess the attributes of endosomes. Thus, in addition to their role in sorting of membrane bound and soluble substances, macrophage endosomes may play a role in the accumulation and transport of molecules resident in the soluble cytoplasm

PROFILE OF PARTICIPANTS IN FISH AND WILDLIFE RELATED OUTDOOR RECREATIONAL ACTIVITIES IN THE UNITED STATES

Resource /Energy Economics and Policy,

Macrophages possess probenecid-inhibitable organic anion transporters that remove fluorescent dyes from the cytoplasmic matrix

We introduced several membrane-impermeant fluorescent dyes, including Lucifer Yellow, carboxyfluorescein, and fura-2, into the cytoplasmic matrix of J774 cells and thioglycollate-elicited mouse peritoneal macrophages by ATP permeabilization of the plasma membrane and observed the subsequent fate of these dyes. The dyes did not remain within the cytoplasmic matrix; instead they were sequestered within phase-lucent cytoplasmic vacuoles and released into the extracellular medium. We used Lucifer Yellow to study these processes further. In cells incubated at 37 degrees C, 87% of Lucifer Yellow was released from the cells within 30 min after dye loading. The dye that remained within the cells at this time was predominantly within cytoplasmic vacuoles. Lucifer yellow transport was temperature dependent and occurred against a concentration gradient; therefore it appeared to be an energy-requiring process. The fluorescent dyes used in these studies are all organic anions. We therefore examined the ability of probenecid (p-[dipropylsulfamoyl]benzoic acid), which blocks organic anion transport across many epithelia, to inhibit efflux of Lucifer Yellow, and found that this drug inhibited this process in a dose-dependent and reversible manner. Efflux of Lucifer Yellow from the cells did not require Na+ co-transport or Cl- antiport; however, it was inhibited by lowering of the extracellular pH. These experiments indicate that macrophages possess probenecid-inhibitable transporters which are similar in their functional properties to organic anion transporters of epithelial cells. Such organic anion transporters have not been described previously in macrophages; they may mediate the release of naturally occurring organic anions such as prostaglandins, leukotrienes, glutathione, bilirubin, or lactate from macrophages

Possible Molecular States of Ds∗Dˉs∗D^{*}_s\bar{D}^{*}_s System and Y(4140)

The interpretation of Y(4140) as a $D^{*}_s\bar{D}^{*}_s$ molecule is studied dynamically in the one boson exchange approach, where $\sigma$, $\eta$ and $\phi$ exchange are included. Ten allowed $D^{*}_s\bar{D}^{*}_s$ states with low spin parity are considered, we find that the $J^{PC}=0^{++}$, $1^{+-}$, $0^{-+}$, $2^{++}$ and $1^{--}$ $D^{*}_s\bar{D}^{*}_s$ configurations are most tightly bound. We suggest the most favorable quantum numbers are $J^{PC}=0^{++}$ for Y(4140) as a $D^{*}_s\bar{D}^{*}_s$ molecule, however, $J^{PC}=0^{-+}$ and $2^{++}$ can not be excluded. We propose to search for the $1^{+-}$ and $1^{--}$ partners in the $J/\psi\eta$ and $J/\psi\eta'$ final states, which is an important test of the molecular hypothesis of Y(4140) and the reasonability of our model. The $0^{++}$ $B^{*}_s\bar{B}^{*}_s$ molecule is deeply bound, experimental search in the $\Upsilon(1S)\phi$ channel at Tevatron and LHC is suggested.Comment: 13 pages,2 figure

The Iowa Homemaker vol.5, no.3-4

Table of Contents Child Study a Part of Homemaking Education by Lulu Lancaster, page 1 A Morning With the Children by Lydia Swanson, page 2 Artificial Feeding by Elizabeth Oldham, page 3 Grade Crossing in Child Life by Dr. Thomas Vance, page 4 Strawberry Days by Arthula Merritt, page 5 An Iowa Home by R. H. Eolbrook, page 5 4-H Page, page 6 With Iowa State Home Economics Association, page 7 Who’s There and Where by Katheryne McCarney, page 8 Editorial, page 9 The Eternal Question, page 10 Toy Making in the Home by Margaret Erickson, page 11 Hot Weather – Cool Food by Louise Corsaut, page 1

Specific Heat of Liquid Helium in Zero Gravity very near the Lambda Point

We report the details and revised analysis of an experiment to measure the specific heat of helium with subnanokelvin temperature resolution near the lambda point. The measurements were made at the vapor pressure spanning the region from 22 mK below the superfluid transition to 4 uK above. The experiment was performed in earth orbit to reduce the rounding of the transition caused by gravitationally induced pressure gradients on earth. Specific heat measurements were made deep in the asymptotic region to within 2 nK of the transition. No evidence of rounding was found to this resolution. The optimum value of the critical exponent describing the specific heat singularity was found to be a = -0.0127+ - 0.0003. This is bracketed by two recent estimates based on renormalization group techniques, but is slightly outside the range of the error of the most recent result. The ratio of the coefficients of the leading order singularity on the two sides of the transition is A+/A- =1.053+ - 0.002, which agrees well with a recent estimate. By combining the specific heat and superfluid density exponents a test of the Josephson scaling relation can be made. Excellent agreement is found based on high precision measurements of the superfluid density made elsewhere. These results represent the most precise tests of theoretical predictions for critical phenomena to date.Comment: 27 Pages, 20 Figure

Chemotaxis: a feedback-based computational model robustly predicts multiple aspects of real cell behaviour

The mechanism of eukaryotic chemotaxis remains unclear despite intensive study. The most frequently described mechanism acts through attractants causing actin polymerization, in turn leading to pseudopod formation and cell movement. We recently proposed an alternative mechanism, supported by several lines of data, in which pseudopods are made by a self-generated cycle. If chemoattractants are present, they modulate the cycle rather than directly causing actin polymerization. The aim of this work is to test the explanatory and predictive powers of such pseudopod-based models to predict the complex behaviour of cells in chemotaxis. We have now tested the effectiveness of this mechanism using a computational model of cell movement and chemotaxis based on pseudopod autocatalysis. The model reproduces a surprisingly wide range of existing data about cell movement and chemotaxis. It simulates cell polarization and persistence without stimuli and selection of accurate pseudopods when chemoattractant gradients are present. It predicts both bias of pseudopod position in low chemoattractant gradients and-unexpectedly-lateral pseudopod initiation in high gradients. To test the predictive ability of the model, we looked for untested and novel predictions. One prediction from the model is that the angle between successive pseudopods at the front of the cell will increase in proportion to the difference between the cell's direction and the direction of the gradient. We measured the angles between pseudopods in chemotaxing Dictyostelium cells under different conditions and found the results agreed with the model extremely well. Our model and data together suggest that in rapidly moving cells like Dictyostelium and neutrophils an intrinsic pseudopod cycle lies at the heart of cell motility. This implies that the mechanism behind chemotaxis relies on modification of intrinsic pseudopod behaviour, more than generation of new pseudopods or actin polymerization by chemoattractant

Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis

Malaria is caused by eukaryotic Plasmodium spp. parasites that classically infect red blood cells. These are difficult organisms to investigate genetically because of their AT-rich genomes. Zhang et al. have exploited this peculiarity by using piggyBac transposon insertion sites to achieve saturation-level mutagenesis for identifying and ranking essential genes and drug targets (see the Perspective by White and Rathod). Genes that are current candidates for drug targets were identified as essential, in contrast to many vaccine target genes. Notably, the proteasome degradation pathway was confirmed as a target for developing therapeutic interventions because of the several essential genes involved and the link to the mechanism of action of the current frontline drug, artemisinin