A critical role for the chromatin remodeller CHD7 in anterior mesoderm during cardiovascular development

CHARGE syndrome is caused by spontaneous loss-of-function mutations to the ATP-dependant chromatin remodeller chromodomain-helicase-DNA-binding protein 7 (CHD7). It is characterised by a distinct pattern of congenital anomalies, including cardiovascular malformations. Disruption to the neural crest lineage has previously been emphasised in the aetiology of this developmental disorder. We present evidence for an additional requirement for CHD7 activity in the Mesp1-expressing anterior mesoderm during heart development. Conditional ablation of Chd7 in this lineage results in major structural cardiovascular defects akin to those seen in CHARGE patients, as well as a striking loss of cardiac innervation and embryonic lethality. Genome-wide transcriptional analysis identified aberrant expression of key components of the Class 3 Semaphorin and Slit-Robo signalling pathways in Chd7(fl/fl);Mesp1-Cre mutant hearts. CHD7 localises at the Sema3c promoter in vivo, with alteration of the local chromatin structure seen following Chd7 ablation, suggestive of direct transcriptional regulation. Furthermore, we uncover a novel role for CHD7 activity upstream of critical calcium handling genes, and demonstrate an associated functional defect in the ability of cardiomyocytes to undergo excitation-contraction coupling. This work therefore reveals the importance of CHD7 in the cardiogenic mesoderm for multiple processes during cardiovascular development

Gauged Flavor Group with Left-Right Symmetry

We construct an anomaly-free extension of the left-right symmetric model, where the maximal flavor group is gauged and anomaly cancellation is guaranteed by adding new vectorlike fermion states. We address the question of the lowest allowed flavor symmetry scale consistent with data. Because of the mechanism recently pointed out by Grinstein et al. tree-level flavor changing neutral currents turn out to play a very weak constraining role. The same occurs, in our model, for electroweak precision observables. The main constraint turns out to come from WR-mediated flavor changing neutral current box diagrams, primarily K - Kbar mixing. In the case where discrete parity symmetry is present at the TeV scale, this constraint implies lower bounds on the mass of vectorlike fermions and flavor bosons of 5 and 10 TeV respectively. However, these limits are weakened under the condition that only SU(2)_R x U(1)_{B-L} is restored at the TeV scale, but not parity. For example, assuming the SU(2) gauge couplings in the ratio gR/gL approx 0.7 allows the above limits to go down by half for both vectorlike fermions and flavor bosons. Our model provides a framework for accommodating neutrino masses and, in the parity symmetric case, provides a solution to the strong CP problem. The bound on the lepton flavor gauging scale is somewhat stronger, because of Big Bang Nucleosynthesis constraints. We argue, however, that the applicability of these constraints depends on the mechanism at work for the generation of neutrino masses.Comment: 1+23 pages, 1 table, 5 figures. v3: some more textual fixes (main change: discussion of Lepton Flavor Violating observables rephrased). Matches journal versio

Declining incidence of malaria imported into the UK from West Africa

BACKGROUND: Two thirds of all falciparum malaria cases reported in the United Kingdom (UK) are acquired in West Africa (WA). To ensure recommendations and guidelines for malaria prophylaxis in travellers to West Africa correlate to the risk of infection, a study was undertaken to examine recent trends and predict future patterns of imported malaria acquired by UK residents visiting West Africa and West African visitors to the UK between 1993 and 2006. METHODS AND RESULTS: Using passenger numbers and malaria surveillance reports, the data revealed a 2.3-fold increase in travel to West Africa with a five-fold increase in travelers visiting friends and relatives (VFR). Malaria incidence fell through the study period, the greatest decline noted in VFR with a fall from 196 cases/1,000 person-years to 52 cases/1,000 person-years, 9.8% per year p < 0.0001. The risk for travellers from the UK visiting for other reasons declined 2.7 fold, at an annual decrease of 7.0%, with the incidence in West African visitors to the UK falling by 2.3 fold, a rate of 7.9% annually. DISCUSSION: The reduction in incidence among all three groups of travellers may be explained by several factors; changing chemoprophylaxis usage and/or increased travel in urban areas where malaria risk has declined over the past decade, or widespread reduction in malaria transmission in West Africa. CONCLUSION: With the reduction in malaria incidence seen in both visitors to and from West Africa, the most rational explanation for these findings is a fall in malaria transmission in West Africa, which may require a change in chemoprophylaxis policy for UK travelers over the next 5-10 years

Caterpillars and fungal pathogens: two co-occurring parasites of an ant-plant mutualism

In mutualisms, each interacting species obtains resources from its partner that it would obtain less efficiently if alone, and so derives a net fitness benefit. In exchange for shelter (domatia) and food, mutualistic plant-ants protect their host myrmecophytes from herbivores, encroaching vines and fungal pathogens. Although selective filters enable myrmecophytes to host those ant species most favorable to their fitness, some insects can by-pass these filters, exploiting the rewards supplied whilst providing nothing in return. This is the case in French Guiana for Cecropia obtusa (Cecropiaceae) as Pseudocabima guianalis caterpillars (Lepidoptera, Pyralidae) can colonize saplings before the installation of their mutualistic Azteca ants. The caterpillars shelter in the domatia and feed on food bodies (FBs) whose production increases as a result. They delay colonization by ants by weaving a silk shield above the youngest trichilium, where the FBs are produced, blocking access to them. This probable temporal priority effect also allows female moths to lay new eggs on trees that already shelter caterpillars, and so to occupy the niche longer and exploit Cecropia resources before colonization by ants. However, once incipient ant colonies are able to develop, they prevent further colonization by the caterpillars. Although no higher herbivory rates were noted, these caterpillars are ineffective in protecting their host trees from a pathogenic fungus, Fusarium moniliforme (Deuteromycetes), that develops on the trichilium in the absence of mutualistic ants. Therefore, the Cecropia treelets can be parasitized by two often overlooked species: the caterpillars that shelter in the domatia and feed on FBs, delaying colonization by mutualistic ants, and the fungal pathogen that develops on old trichilia. The cost of greater FB production plus the presence of the pathogenic fungus likely affect tree growth

Change in Composition of the Anopheles Gambiae Complex and its Possible Implications for the Transmission of Malaria and Lymphatic Filariasis in North-Eastern Tanzania.

A dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania. The study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2-4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR. As in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species. The study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area

A ‘quiet revolution’? The impact of Training Schools on initial teacher training partnerships

This paper discusses the impact on initial teacher training of a new policy initiative in England: the introduction of Training Schools. First, the Training School project is set in context by exploring the evolution of a partnership approach to initial teacher training in England. Ways in which Training Schools represent a break with established practice are considered together with their implications for the dominant mode of partnership led by higher education institutions (HEIs). The capacity of Training Schools to achieve their own policy objectives is examined, especially their efficacy as a strategy for managing innovation and the dissemination of innovation. The paper ends by focusing on a particular Training School project which has adopted an unusual approach to its work and enquires whether this alternative approach could offer a more profitable way forward. During the course of the paper, five different models of partnership are considered: collaborative, complementary, HEI-led, school-led and partnership within a partnership

Motivation and Motor Control: Hemispheric Specialization for Approach Motivation Reverses with Handedness

(SSH), according to which the hemispheric laterality of affective motivation depends on the laterality of motor control for the dominant hand (i.e., the “sword hand," used preferentially to perform approach actions) and the nondominant hand (i.e., the “shield hand," used preferentially to perform avoidance actions).To determine whether the laterality of approach motivation varies with handedness, we measured alpha-band power (an inverse index of neural activity) in right- and left-handers during resting-state electroencephalography and analyzed hemispheric alpha-power asymmetries as a function of the participants' trait approach motivational tendencies. Stronger approach motivation was associated with more left-hemisphere activity in right-handers, but with more right-hemisphere activity in left-handers.The hemispheric correlates of approach motivation reversed between right- and left-handers, consistent with the way they typically use their dominant and nondominant hands to perform approach and avoidance actions. In both right- and left-handers, approach motivation was lateralized to the same hemisphere that controls the dominant hand. This covariation between neural systems for action and emotion provides initial support for the SSH

Surgical treatment of zygomatic bone fracture using two points fixation versus three point fixation-a randomised prospective clinical trial

<p>Abstract</p> <p>Background</p> <p>The zygoma plays an important role in the facial contour for both cosmetic and functional reasons; therefore zygomatic bone injuries should be properly diagnosed and adequately treated. Comparison of various surgical approaches and their complications can only be done objectively using outcome measurements which in turn require protocol management and long-term follow up. The preference for open reduction and internal fixation of zygomatic fractures at three points has continued to grow in response to observations of inadequate results from two point and one point fixation techniques.</p> <p>The objectives of this study were to compare the efficacy of zygomatic bone after treatment with ORIF using 2 point fixation and ORIF using 3 point fixation and compare the outcome of two procedures.</p> <p>Methods</p> <p>100 patients were randomly divided equally into two groups. In group A, 50 patients were treated by ORIF using two point fixation by miniplates and in group B, 50 patients were treated by ORIF using three point fixation by miniplates. They were evaluated for their complications during and after surgery with their advantages and disadvantages and the difference between the two groups was observed.</p> <p>Results</p> <p>A total of 100 fractures were sustained. We found that postoperative complication like decreased malar height and vertical dystopia was more common in those patients who were treated by two point fixation than those who were treated with three point fixation.</p> <p>Conclusions</p> <p>Based on this study open reduction and internal fixation using three point fixation by miniplates is the best available method for the treatment zygomatic bone fractures.</p

Fluids in cosmology

We review the role of fluids in cosmology by first introducing them in General Relativity and then by applying them to a FRW Universe's model. We describe how relativistic and non-relativistic components evolve in the background dynamics. We also introduce scalar fields to show that they are able to yield an inflationary dynamics at very early times (inflation) and late times (quintessence). Then, we proceed to study the thermodynamical properties of the fluids and, lastly, its perturbed kinematics. We make emphasis in the constrictions of parameters by recent cosmological probes.Comment: 34 pages, 4 figures, version accepted as invited review to the book "Computational and Experimental Fluid Mechanics with Applications to Physics, Engineering and the Environment". Version 2: typos corrected and references expande