Correlation functions quantify super-resolution images and estimate apparent clustering due to over-counting

We present an analytical method to quantify clustering in super-resolution localization images of static surfaces in two dimensions. The method also describes how over-counting of labeled molecules contributes to apparent self-clustering and how the effective lateral resolution of an image can be determined. This treatment applies to clustering of proteins and lipids in membranes, where there is significant interest in using super-resolution localization techniques to probe membrane heterogeneity. When images are quantified using pair correlation functions, the magnitude of apparent clustering due to over-counting will vary inversely with the surface density of labeled molecules and does not depend on the number of times an average molecule is counted. Over-counting does not yield apparent co-clustering in double label experiments when pair cross-correlation functions are measured. We apply our analytical method to quantify the distribution of the IgE receptor (Fc{\epsilon}RI) on the plasma membranes of chemically fixed RBL-2H3 mast cells from images acquired using stochastic optical reconstruction microscopy (STORM) and scanning electron microscopy (SEM). We find that apparent clustering of labeled IgE bound to Fc{\epsilon}RI detected with both methods arises from over-counting of individual complexes. Thus our results indicate that these receptors are randomly distributed within the resolution and sensitivity limits of these experiments.Comment: 22 pages, 5 figure

The "Ram Effect": A "Non-Classical" Mechanism for Inducing LH Surges in Sheep

During spring sheep do not normally ovulate but exposure to a ram can induce ovulation. In some ewes an LH surge is induced immediately after exposure to a ram thus raising questions about the control of this precocious LH surge. Our first aim was to determine the plasma concentrations of oestradiol (E2) E2 in anoestrous ewes before and after the "ram effect" in ewes that had a "precocious" LH surge (starting within 6 hours), a "normal" surge (between 6 and 28h) and "late» surge (not detected by 56h). In another experiment we tested if a small increase in circulating E2 could induce an LH surge in anoestrus ewes. The concentration of E2 significantly was not different at the time of ram introduction among ewes with the three types of LH surge. "Precocious" LH surges were not preceded by a large increase in E2 unlike "normal" surges and small elevations of circulating E2 alone were unable to induce LH surges. These results show that the "precocious" LH surge was not the result of E2 positive feedback. Our second aim was to test if noradrenaline (NA) is involved in the LH response to the "ram effect". Using double labelling for Fos and tyrosine hydroxylase (TH) we showed that exposure of anoestrous ewes to a ram induced a higher density of cells positive for both in the A1 nucleus and the Locus Coeruleus complex compared to unstimulated controls. Finally, the administration by retrodialysis into the preoptic area, of NA increased the proportion of ewes with an LH response to ram odor whereas treatment with the α1 antagonist Prazosin decreased the LH pulse frequency and amplitude induced by a sexually active ram. Collectively these results suggest that in anoestrous ewes NA is involved in ram-induced LH secretion as observed in other induced ovulators

Therapeutic efficacy of chloroquine for treatment of Plasmodium vivax malaria cases in Halaba district, South Ethiopia

<p>Abstract</p> <p>Background</p> <p>Chloroquine is an anti-malarial drug being used to treat <it>Plasmodium vivax </it>malaria cases in Ethiopia. However, emergence of chloroquine resistant strains of the parasite has challenged the current efficacy of the drug. Therefore, the aim of this study was to assess the effectiveness of chloroquine against <it>P. vivax </it>strains in one of the malaria endemic areas of Ethiopia, namely Halaba district, located in South Nations and Nationalities Peoples Region (SNNPR) of South Ethiopia</p> <p>Results</p> <p>Among 87 malaria patients enrolled in the study, only 80 of them completed the 28-days follow-up. Seven of them dropped from the study for different reasons. Among those study participants that completed their follow-up, 69 were classified under the category of adequate clinical and parasitological response (ACPR). However, the remaining 11 cases were considered as under treatment failure mainly due to recurrence of parasitemia on day 7 (four patients), day 14 (six patients), and day 21 (one patient). The age of all cases of treatment failures was found to be less than 20 years. The load of parasitemia of patients with treatment failure on day of admission (4709.4/μl) was higher than day of recurrence (372.37/μl). Parasite reduction ratio (PRR) of treatment failure cases was 12.6/μl.</p> <p>Conclusion</p> <p>This report revealed the rise in treatment failure (13% [95% CI = 0.074 - 0.217]) as compared to earlier reports from Ethiopia. It signals the spreading of chloroquine resistant <it>P. vivax </it>(CRPv) strains to malaria endemic areas of Ethiopia. It is recommended that all concerned bodies should act aggressively before further expansion of the current drug resistant malaria.</p

Diagnosis of Human Visceral Pentastomiasis

Visceral pentastomiasis in humans is caused by the larval stages (nymphs) of the arthropod-related tongue worms Linguatula serrata, Armillifer armillatus, A. moniliformis, A. grandis, and Porocephalus crotali. The majority of cases has been reported from Africa, Malaysia, and the Middle East, where visceral pentastomiasis may be an incidental finding in autopsies, and less often from China and Latin America. In Europe and North America, the disease is only rarely encountered in immigrants and long-term travelers, and the parasitic lesions may be confused with malignancies, leading to a delay in the correct diagnosis. Since clinical symptoms are variable and serological tests are not readily available, the diagnosis often relies on histopathological examinations. This laboratory symposium focuses on the diagnosis of this unusual parasitic disease and presents its risk factors and epidemiology

Antigen-specific influence of GM/KM allotypes on IgG isotypes and association of GM allotypes with susceptibility to Plasmodium falciparum malaria

<p>Abstract</p> <p>Background</p> <p><it>Plasmodium falciparum </it>malaria is a complex disease in which genetic and environmental factors influence susceptibility. IgG isotypes are in part genetically controlled, and GM/KM allotypes are believed to be involved in this control.</p> <p>Methods</p> <p>In this study, 216 individuals from Daraweesh, an area of seasonal malaria transmission in Sudan, were followed for nine years for malaria infection. Total IgG and IgG isotypes against four malaria antigens, MSP2-3D7, MSP2-FC27, AMA1, and Pf332-C231 were measured in plasma obtained from the cohort at the end of the study, during the dry malaria-free period. The GM/KM allotypes of the donors were determined.</p> <p>Results</p> <p>The GM 1,17 5,13,14,6 phenotype was associated with a higher incidence of malaria compared with the non-1,17 5,13,14,6 phenotypes (P = 0.037). Paradoxically, the carriers of the GM 1,17 5,13,14,6 phenotype had significantly higher baseline levels of total IgG and non-cytophilic IgG isotypes as compared to non-carriers. The KM allotypes influence on IgG isotypes level was limited. Finally, the differences in the baseline concentrations of total IgG and IgG isotypes between the different GK/KM phenotype carriers were antigen-dependent.</p> <p>Discussion</p> <p>The results show that GM but not KM allotypes appeared to influence host susceptibility to uncomplicated malaria as well as the antibody profile of the donors, and the carriers of the GM 1,17 5,13,14,6 phenotype were the most susceptible</p> <p>Conclusions</p> <p>The GM allotypes have significant influence on susceptibility to uncomplicated <it>P. falciparum </it>malaria and antigen-dependent influence on total IgG and IgG subclasses.</p

Joint angle variability and co-variation in a reaching with a rod task

The problem at the heart of motor control is how the myriad units of the neuromotor system are coordinated to perform goal-directed movements. Although for long these numerous degrees of freedom (DOFs) were considered redundant, recent views emphasize more that the DOFs should be considered abundant, allowing flexible performance. We studied how variability in arm joints was employed to stabilize the displaced end-effector in tool use to examine how the neuromotor system flexibly exploits DOFs in the upper extremity. Participants made pointing movements with the index finger and with the index finger extended by rods of 10, 20, and 30 cm. Using the uncontrolled manifold (UCM) method, the total joint angle variance was decomposed into two parts, the joint angle variance that did not affect the position of the end-effector (VUCM) and the variance that results in a deviation of the position of the end-effector from its mean (VORT). Analyses showed that some angles depended on length of the rod in use. For all rod lengths, VUCM was larger than VORT, and this did not differ over rod lengths, demonstrating that the arm was organized into a synergy. Finally, the variation in the joint angles in the arm as well as the degree of co-variation between these angles did not differ for the rod’s tip and the hand. We concluded that synergies are formed in the arm during reaching with an extended end-effector and those synergies stabilize different parts of the arm+rod system equally

Beyond the required LISA free-fall performance: new LISA pathfinder results down to 20 μHz

In the months since the publication of the first results, the noise performance of LISA Pathfinder has improved because of reduced Brownian noise due to the continued decrease in pressure around the test masses, from a better correction of noninertial effects, and from a better calibration of the electrostatic force actuation. In addition, the availability of numerous long noise measurement runs, during which no perturbation is purposely applied to the test masses, has allowed the measurement of noise with good statistics down to 20  μHz. The Letter presents the measured differential acceleration noise figure, which is at (1.74±0.05)  fm s^{-2}/sqrt[Hz] above 2 mHz and (6±1)×10  fm s^{-2}/sqrt[Hz] at 20  μHz, and discusses the physical sources for the measured noise. This performance provides an experimental benchmark demonstrating the ability to realize the low-frequency science potential of the LISA mission, recently selected by the European Space Agency

A bovine lymphosarcoma cell line infected with theileria annulata exhibits an irreversible reconfiguration of host cell gene expression

Theileria annulata, an intracellular parasite of bovine lymphoid cells, induces substantial phenotypic alterations to its host cell including continuous proliferation, cytoskeletal changes and resistance to apoptosis. While parasite induced modulation of host cell signal transduction pathways and NFκB activation are established, there remains considerable speculation on the complexities of the parasite directed control mechanisms that govern these radical changes to the host cell. Our objectives in this study were to provide a comprehensive analysis of the global changes to host cell gene expression with emphasis on those that result from direct intervention by the parasite. By using comparative microarray analysis of an uninfected bovine cell line and its Theileria infected counterpart, in conjunction with use of the specific parasitacidal agent, buparvaquone, we have identified a large number of host cell gene expression changes that result from parasite infection. Our results indicate that the viable parasite can irreversibly modify the transformed phenotype of a bovine cell line. Fifty percent of genes with altered expression failed to show a reversible response to parasite death, a possible contributing factor to initiation of host cell apoptosis. The genes that did show an early predicted response to loss of parasite viability highlighted a sub-group of genes that are likely to be under direct control by parasite infection. Network and pathway analysis demonstrated that this sub-group is significantly enriched for genes involved in regulation of chromatin modification and gene expression. The results provide evidence that the Theileria parasite has the regulatory capacity to generate widespread change to host cell gene expression in a complex and largely irreversible manner