cAMP-Signalling Regulates Gametocyte-Infected Erythrocyte Deformability Required for Malaria Parasite Transmission.

Blocking Plasmodium falciparum transmission to mosquitoes has been designated a strategic objective in the global agenda of malaria elimination. Transmission is ensured by gametocyte-infected erythrocytes (GIE) that sequester in the bone marrow and at maturation are released into peripheral blood from where they are taken up during a mosquito blood meal. Release into the blood circulation is accompanied by an increase in GIE deformability that allows them to pass through the spleen. Here, we used a microsphere matrix to mimic splenic filtration and investigated the role of cAMP-signalling in regulating GIE deformability. We demonstrated that mature GIE deformability is dependent on reduced cAMP-signalling and on increased phosphodiesterase expression in stage V gametocytes, and that parasite cAMP-dependent kinase activity contributes to the stiffness of immature gametocytes. Importantly, pharmacological agents that raise cAMP levels in transmissible stage V gametocytes render them less deformable and hence less likely to circulate through the spleen. Therefore, phosphodiesterase inhibitors that raise cAMP levels in P. falciparum infected erythrocytes, such as sildenafil, represent new candidate drugs to block transmission of malaria parasites

A compendium and functional characterization of mammalian genes involved in adaptation to Arctic or Antarctic environments

Many mammals are well adapted to surviving in extremely cold environments. These species have likely accumulated genetic changes that help them efficiently cope with low temperatures. It is not known whether the same genes related to cold adaptation in one species would be under selection in another species. The aims of this study therefore were: to create a compendium of mammalian genes related to adaptations to a low temperature environment; to identify genes related to cold tolerance that have been subjected to independent positive selection in several species; to determine promising candidate genes/pathways/organs for further empirical research on cold adaptation in mammals

Search for CP violation in D0 and D+ decays

A high statistics sample of photoproduced charm particles from the FOCUS (E831) experiment at Fermilab has been used to search for CP violation in the Cabibbo suppressed decay modes D+ to K-K+pi+, D0 to K-K+ and D0 to pi-pi+. We have measured the following CP asymmetry parameters: A_CP(K-K+pi+) = +0.006 +/- 0.011 +/- 0.005, A_CP(K-K+) = -0.001 +/- 0.022 +/- 0.015 and A_CP(pi-pi+) = +0.048 +/- 0.039 +/- 0.025 where the first error is statistical and the second error is systematic. These asymmetries are consistent with zero with smaller errors than previous measurements.Comment: 12 pages, 4 figure

Notch and MAML-1 Complexation Do Not Detectably Alter the DNA Binding Specificity of the Transcription Factor CSL

Canonical Notch signaling is initiated when ligand binding induces proteolytic release of the intracellular part of Notch (ICN) from the cell membrane. ICN then travels into the nucleus where it drives the assembly of a transcriptional activation complex containing the DNA-binding transcription factor CSL, ICN, and a specialized co-activator of the Mastermind family. A consensus DNA binding site motif for the CSL protein was previously defined using selection-based methods, but whether subsequent association of Notch and Mastermind-like proteins affects the DNA binding preferences of CSL has not previously been examined.Here, we utilized protein-binding microarrays (PBMs) to compare the binding site preferences of isolated CSL with the preferred binding sites of CSL when bound to the CSL-binding domains of all four different human Notch receptors. Measurements were taken both in the absence and in the presence of Mastermind-like-1 (MAML1). Our data show no detectable difference in the DNA binding site preferences of CSL before and after loading of Notch and MAML1 proteins.These findings support the conclusion that accrual of Notch and MAML1 promote transcriptional activation without dramatically altering the preferred sites of DNA binding, and illustrate the potential of PBMs to analyze the binding site preferences of multiprotein-DNA complexes

A Study of D0 --> K0(S) K0(S) X Decay Channels

Using data from the FOCUS experiment (FNAL-E831), we report on the decay of $D^0$ mesons into final states containing more than one $K^0_S$. We present evidence for two Cabibbo favored decay modes, $D^0\to K^0_SK^0_S K^- \pi^+$ and $D^0\to K^0_SK^0_S K^+ \pi^-$, and measure their combined branching fraction relative to $D^0\to \bar{K} ^0\pi^+\pi^-$ to be $\frac{\Gamma(D^0\to K^0_SK^0_SK^{\pm}\pi^{\mp})}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0106 $\pm$ 0.0019 $\pm$ 0.0010. Further, we report new measurements of $\frac{\Gamma(D^0\to K^0_SK^0_SK^0_S)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0179 $\pm$ 0.0027 $\pm$ 0.0026, $\frac{\Gamma(D^0\to K^0\bar{K} ^0)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0144 $\pm$ 0.0032 $\pm$ 0.0016, and $\frac{\Gamma(D^0\to K^0_SK^0_S\pi^+\pi^-)}{\Gamma(D^0\to \bar{K} ^0\pi^+\pi^-)}$ = 0.0208 $\pm$ 0.0035 $\pm$ 0.0021 where the first error is statistical and the second is systematic.Comment: 11 pages, 3 figures, typos correcte

Integrating transposable elements in the 3D genome

Chromosome organisation is increasingly recognised as an essential component of genome regulation, cell fate and cell health. Within the realm of transposable elements (TEs) however, the spatial information of how genomes are folded is still only rarely integrated in experimental studies or accounted for in modelling. Whilst polymer physics is recognised as an important tool to understand the mechanisms of genome folding, in this commentary we discuss its potential applicability to aspects of TE biology. Based on recent works on the relationship between genome organisation and TE integration, we argue that existing polymer models may be extended to create a predictive framework for the study of TE integration patterns. We suggest that these models may offer orthogonal and generic insights into the integration profiles (or "topography") of TEs across organisms. In addition, we provide simple polymer physics arguments and preliminary molecular dynamics simulations of TEs inserting into heterogeneously flexible polymers. By considering this simple model, we show how polymer folding and local flexibility may generically affect TE integration patterns. The preliminary discussion reported in this commentary is aimed to lay the foundations for a large-scale analysis of TE integration dynamics and topography as a function of the three-dimensional host genome

Protein supplementation in strength and conditioning adepts: knowledge, dietary behaviour and practice in Palermo, Italy

Background: It is known that supplement use is a widespread and accepted practice by athletes and people who attend commercial gyms. Little is known about protein supplement amongst people undertaking strength training in commercial gyms in Italy when compared to the US. Objective: The purpose of this study was to examine the use of protein supplementation, alone or in association with other supplements, and dietary behavior amongst regular fitness center attendees in Palermo, Italy. Design: Resistance training information have been collected from 800 regular fitness center attendees for the initial analysis. A specific questionnaire was generated for the experimentation. Data were collected using a face-to-face interview method. Supplement users were then compared to the non users and analyzed using a one-way ANOVA, Kruskall-Wallis, chi-square test or exact test of Fisher when appropriate. Results: 30.1% of the respondents use dietary supplements during their training as a believe it is the "way to gain muscles and strength". Whey protein shakes (50.0%) mixed with creatine and amino-acids (48.3%) were the most frequent choices amongst the users. A majority of the subjects (34.0%) appeared to rely on their gym instructors' advice for their intake; a lower proportion (13.0%) consulted physicians, while none of them consulted nutritionists. A high consumption of milk has been noticed in both users (67,7%) and non-users (52,8%); supplement non-users consumed significantly more snacks and bakery products than users per week (P < 0.001), while users consumed significantly more protein-rich foods (P < 0.01) with a particular preference for meat (48.0%). Conclusions: A considerable number of regular strength training adepts consume protein supplements mixed with other products (mainly creatine and amino-acids). Limited numbers consult "dietary specialists" and rely mainly on their instructors. We emphasize on the importance of the dissemination of scientifically based information about supplementation in this environment and the promotion of updated educational programs for the instructors

Sentinel node biopsy for breast cancer: is it already a standard of care? A survey of current practice in an Italian region

BACKGROUND: Although sentinel node biopsy (SNB) is becoming the standard approach for axillary staging in patients with small breast cancer, criteria for patient selection and some technical aspects of the procedure have yet to be clearly defined. The aim of the present survey was therefore to investigate the way in which SNB is used by general surgeons working in the Veneto region, Italy. METHODS: A 29-item questionnaire regarding various aspects of SNB practice was mailed to surgeons in charge of breast surgery in all the 56 surgical centres of the region. RESULTS: The rate of response to the questionnaire was 82.1% (n = 46); 69.6% (n = 32) of the respondents routinely perform SNB in their clinical practice. Most of the interviewed surgeons (93.5%) expressed the belief that the acceptable false negative rate should be ≤5%. However, among the surgeons who perform SNB, only 34.4% performed more than 20 SNB during the learning phase. Indications are limited to tumours of ≤1 cm by 31.2% (n = 10) of respondents, ≤2 cm by 46.9% (n = 15) and ≤3 cm by 21.9% (n = 7). Almost all respondents (93.7%) agreed that a clinically positive axilla is a contraindication to SNB, while opinions differed widely concerning other potential contraindications. In most of the centres considered, SN identification is undertaken on the day before surgery using a subdermal injection of 30–50 MBq of 99mTc-albumin-nanocolloid followed by lymphoscintigraphy. CONCLUSIONS: SNB is currently performed in the majority of hospitals in the Veneto region. However, the training phase and criteria used for patient selection differ from centre to centre. Certified training courses and shared guidelines are therefore highly desirable

Recycled gabbro signature in hotspot magmas unveiled by plume–ridge interactions

Lavas erupted within plate interiors above upwelling mantle plumes have chemical signatures that are distinct from midocean ridge lavas. When a plume interacts with a mid-ocean ridge, the compositions of both their lavas changes, but there is no consensus as to how this interaction occurs1–3. For the past 15 Myr, the Pacific–Antarctic mid-ocean ridge has been approaching the Foundation hotspot4 and erupted lavas have formed seamounts. Here we analyse the noble gas isotope and trace element signature of lava samples collected from the seamounts. We find that both intraplate and on-axis lavas have noble gas isotope signatures consistent with the contribution from a primitive plume source. In contrast, nearaxis lavas show no primitive noble gas isotope signatures, but are enriched in strontium and lead, indicative of subducted former oceanic lower crust melting within the plume source5–7. We propose that, in a near-ridge setting, primitive, plumesourced magmas formed deep in the plume are preferentially channelled to and erupted at the ridge-axis. The remaining residue continues to rise and melt, forming the near-axis seamounts. With the deep melts removed, the geochemical signature of subduction contained within the residue becomes apparent. Lavas with strontium and lead enrichments are found worldwide where plumes meet mid-ocean ridges6–8, suggesting that subducted lower crust is an important but previously unrecognised plume component