Myosin II filament dynamics in actin networks revealed with interferometric scattering microscopy

The plasma membrane and the underlying cytoskeletal cortex constitute active platforms for a variety of cellular processes. Recent work has shown that the remodeling acto-myosin network modifies local membrane organization, but the molecular details are only partly understood due to difficulties with experimentally accessing the relevant time and length scales. Here, we use interferometric scattering (iSCAT) microscopy to investigate a minimal acto-myosin network linked to a supported lipid bilayer membrane. Using the magnitude of the interferometric contrast, which is proportional to molecular mass, and fast acquisition rates, we detect, and image individual membrane attached actin filaments diffusing within the acto-myosin network and follow individual myosin II filament dynamics. We quantify myosin II filament dwell times and processivity as functions of ATP concentration, providing experimental evidence for the predicted ensemble behavior of myosin head domains. Our results show how decreasing ATP concentrations lead to both increasing dwell times of individual myosin II filaments and a global change from a remodeling to a contractile state of the acto-myosin network

Intrinsic Photoconductivity of Ultracold Fermions in Optical Lattices

We report on the experimental observation of an analog to a persistent alternating photocurrent in an ultracold gas of fermionic atoms in an optical lattice. The dynamics is induced and sustained by an external harmonic confinement. While particles in the excited band exhibit long-lived oscillations with a momentum dependent frequency a strikingly different behavior is observed for holes in the lowest band. An initial fast collapse is followed by subsequent periodic revivals. Both observations are fully explained by mapping the system onto a nonlinear pendulum.Comment: 5+7 pages, 4+4 figure

Multi-Locus Phylogenetic Analyses of the Almadablennius Clade Reveals Inconsistencies with the Present Taxonomy of Blenniid Fishes

We used a multi-locus phylogenetic approach (i.e., combining both mitochondrial and nuclear DNA fragments) to address some long-standing taxonomic inconsistencies within the diverse fish clade of Combtooth Blennies (Blenniidae—unranked clade Almadablennius). The obtained phylogenetic trees revealed some major inconsistencies in the current taxonomy of Parablennini, such as the paraphyletic status of the Salaria and Parablennius genera, casting some doubt regarding their actual phylogenetic relationship. Furthermore, a scarce-to-absent genetic differentiation was observed among the three species belonging to the genus Chasmodes. This study provides an updated taxonomy and phylogeny of the former genus Salaria, ascribing some species to the new genus Salariopsis gen. nov., and emphasizes the need for a revision of the genus Parablennius

Formative evaluation of a training intervention for community health workers in South Africa : a before and after study

Background Community Health Workers (CHWs) have a crucial role in improving health in their communities and their role is being expanded in many parts of the world. However, the effectiveness of CHWs is limited by poor training and the education of CHWs has received little scientific attention. Methods Our study was carried out in two districts of KwaZulu-Natal, South Africa. We developed and piloted an inexpensive (two day) training intervention covering national government priorities: HIV/AIDS, sexually transmitted disease and Tuberculosis; and Women’s Sexual and Reproductive Health and Rights. Sixty-four CHWs consented to participate in the main study which measured knowledge gains using a modified Solomon design of four different testing schedules to distinguish between the effects of the intervention, testing and any interaction between intervention and testing. We also measured confidence, satisfaction and costs. Results Following the training intervention, improvements in knowledge scores were seen across topics and across districts. These changes in knowledge were statistically significant (p<0.001) and of large magnitude (over 45 percentage points or four standard deviations). However, the CHWs assigned to the test-test-train schedule in one district showed high gains in knowledge prior to receiving the training. All CHWs reported high levels of satisfaction with the training and marked improvements in their confidence in advising clients. The training cost around US$48 per CHW per day and has the potential to be cost-effective if the large gains in knowledge are translated into improved field-based performance and thus health outcomes. Conclusion Training CHWs can result in large improvements in knowledge with a short intervention. However, improvements seen in other studies could be due to test ‘reactivity’. Further work is needed to measure the generalisability of our results, retention of knowledge and the extent to which improved knowledge is translated into improved practice

PSGL-1 engagement by E-selectin signals through Src kinase Fgr and ITAM adapters DAP12 and FcRγ to induce slow leukocyte rolling

E-selectin binding to P-selectin glycoprotein ligand-1 (PSGL-1) can activate the β2 integrin lymphocyte function-associated antigen-1 by signaling through spleen tyrosine kinase (Syk). This signaling is independent of Gαi-protein–coupled receptors, results in slow rolling, and promotes neutrophil recruitment to sites of inflammation. However, the signaling pathways linking E-selectin engagement of PSGL-1 to Syk activation are unknown. To test the role of Src family kinases and immunoreceptor tyrosine-based activating motif (ITAM)–containing adaptor proteins, we used different gene-deficient mice in flow chamber, intravital microscopy, and peritonitis studies. E-selectin–mediated phosphorylation of Syk and slow rolling was abolished in neutrophils from fgr−/− or hck−/− lyn−/− fgr−/− mice. Neutrophils from Tyrobp−/− Fcrg−/− mice lacking both DAP12 and FcRγ were incapable of sustaining slow neutrophil rolling on E-selectin and intercellular adhesion molecule-1 and were unable to phosphorylate Syk and p38 MAPK. This defect was confirmed in vivo by using mixed chimeric mice. Gαi-independent neutrophil recruitment into the inflamed peritoneal cavity was sharply suppressed in Tyrobp−/− Fcrg−/− mice. Our data demonstrate that an ITAM-dependent pathway involving the Src-family kinase Fgr and the ITAM-containing adaptor proteins DAP12 and FcRγ is involved in the initial signaling events downstream of PSGL-1 that are required to initiate neutrophil slow rolling

Exciton spin relaxation in single semiconductor quantum dots

We study the relaxation of the exciton spin (longitudinal relaxation time $T_{1}$) in single asymmetrical quantum dots due to an interplay of the short--range exchange interaction and acoustic phonon deformation. The calculated relaxation rates are found to depend strongly on the dot size, magnetic field and temperature. For typical quantum dots and temperatures below 100 K, the zero--magnetic field relaxation times are long compared to the exciton lifetime, yet they are strongly reduced in high magnetic fields. We discuss explicitly quantum dots based on (In,Ga)As and (Cd,Zn)Se semiconductor compounds.Comment: accepted for Phys. Rev.

Clinical development of placental malaria vaccines and immunoassays harmonization:a workshop report

International audiencePlacental malaria caused by Plasmodium falciparum infection constitutes a major health problem manifesting as severe disease and anaemia in the mother, impaired fetal development, low birth weight or spontaneous abortion. Prevention of placental malaria currently relies on two key strategies that are losing efficacy due to spread of resistance: long-lasting insecticide-treated nets and intermittent preventive treatment during pregnancy. A placental malaria vaccine would be an attractive, cost-effective complement to the existing control tools. Two placental malaria vaccine candidates are currently in Phase Ia/b clinical trials. During two workshops hosted by the European Vaccine Initiative, one in Paris in April 2014 and the other in Brussels in November 2014, the main actors in placental malaria vaccine research discussed the harmonization of clinical development plans and of the immunoassays with a goal to define standards that will allow comparative assessment of different placental malaria vaccine candidates. The recommendations of these workshops should guide researchers and clinicians in the further development of placental malaria vaccines

A cross-sectional study of vascular risk factors in a rural South African population : data from the Southern African Stroke Prevention Initiative (SASPI)

Background: Rural sub-Saharan Africa is at an early stage of economic and health transition. It is predicted that the 21st century will see a serious added economic burden from non-communicable disease including vascular disease in low-income countries as they progress through the transition. The stage of vascular disease in a population is thought to result from the prevalence of vascular risk factors. Already hypertension and stroke are common in adults in sub-Saharan Africa. Using a multidisciplinary approach we aimed to assess the prevalence of several vascular risk factors in Agincourt, a rural demographic surveillance site in South Africa. Methods: We performed a cross sectional random sample survey of adults aged over 35 in Agincourt (population ≈ 70 000). Participants were visited at home by a trained nurse who administered a questionnaire, carried out clinical measurements and took a blood sample. From this we assessed participants' history of vascular risk, blood pressure using an OMRON 705 CP monitor, waist circumference, body mass index (BMI), ankle brachial index (ABI), and total and HDL cholesterol. Results: 402 people (24% men) participated. There was a high prevalence of smoking in men, but the number of cigarettes smoked was small. There was a striking difference in mean BMI between men and women (22.8 kg/m2 versus 27.2 kg/m2), but levels of blood pressure were very similar. 43% of participants had a blood pressure greater than 140/90 or were on anti-hypertensive treatment and 37% of participants identified with measured high blood pressure were on pharmacological treatment. 12% of participants had an ABI of < 0.9, sugesting the presence of sub-clinical atheroma. 25.6% of participants had a total cholesterol level > 5 mmol/l. Conclusion: We found a high prevalence of hypertension, obesity in women, and a suggestion of subclinical atheroma despite relatively favourable cholesterol levels in a rural South African population. South Africa is facing the challenge of an emerging epidemic of vascular disease. Research to establish the social determinates of these risk factors and interventions to reduce both individual and population risk are required

Preoperative computed tomography staging of nonmetastatic colon cancer predicts outcome: implications for clinical trials

Colon cancer patients routinely undergo preoperative computed tomography (CT) scanning, but local staging is thought to be inaccurate. We aimed to determine if clinical outcome could be predicted from radiological features of the primary tumour. Consecutive patients at one hospital undergoing primary resection for colon cancer during 2000–2004 were included. Patients with visible metastases were excluded. Preoperative CT scans were reviewed independently by two radiologists blinded to histological stage and outcome. Images of the primary tumour were evaluated according to conventional TNM criteria and patients were stratified into ‘good' or ‘poor' prognosis groups. Comparison was made between prognostic group and actual clinical outcome. Hundred and twenty-six preoperative CT scans were reviewed. T-stage and nodal status was correctly predicted in only 60 and 62%, respectively. However, inter-observer agreement for prognostic group was 79% (κ=0.59) and 3-year relapse-free survival was 71 and 43% for the CT-predicted ‘good' and ‘poor' groups, respectively (P<0.0066). This compared favourably with 75 vs 43% for histology-predicted prognostic groups. Computed tomography is a robust method for stratifying patients preoperatively, with similar accuracy to histopathology for predicting outcome. Recognition of poor prognosis tumours preoperatively may permit investigation into the future use of neo-adjuvant therapy in colon cancer