Eosinophils Are Important for Protection, Immunoregulation and Pathology during Infection with Nematode Microfilariae

Eosinophil responses typify both allergic and parasitic helminth disease. In helminthic disease, the role of eosinophils can be both protective in immune responses and destructive in pathological responses. To investigate whether eosinophils are involved in both protection and pathology during filarial nematode infection, we explored the role of eosinophils and their granule proteins, eosinophil peroxidase (EPO) and major basic protein-1 (MBP-1), during infection with Brugia malayi microfilariae. Using eosinophil-deficient mice (PHIL), we further clarify the role of eosinophils in clearance of microfilariae during primary, but not challenge infection in vivo. Deletion of EPO or MBP-1 alone was insufficient to abrogate parasite clearance suggesting that either these molecules are redundant or eosinophils act indirectly in parasite clearance via augmentation of other protective responses. Absence of eosinophils increased mast cell recruitment, but not other cell types, into the broncho-alveolar lavage fluid during challenge infection. In addition absence of eosinophils or EPO alone, augmented parasite-induced IgE responses, as measured by ELISA, demonstrating that eosinophils are involved in regulation of IgE. Whole body plethysmography indicated that nematode-induced changes in airway physiology were reduced in challenge infection in the absence of eosinophils and also during primary infection in the absence of EPO alone. However lack of eosinophils or MBP-1 actually increased goblet cell mucus production. We did not find any major differences in cytokine responses in the absence of eosinophils, EPO or MBP-1. These results reveal that eosinophils actively participate in regulation of IgE and goblet cell mucus production via granule secretion during nematode-induced pathology and highlight their importance both as effector cells, as damage-inducing cells and as supervisory cells that shape both innate and adaptive immunity

Impact Factor: outdated artefact or stepping-stone to journal certification?

A review of Garfield's journal impact factor and its specific implementation as the Thomson Reuters Impact Factor reveals several weaknesses in this commonly-used indicator of journal standing. Key limitations include the mismatch between citing and cited documents, the deceptive display of three decimals that belies the real precision, and the absence of confidence intervals. These are minor issues that are easily amended and should be corrected, but more substantive improvements are needed. There are indications that the scientific community seeks and needs better certification of journal procedures to improve the quality of published science. Comprehensive certification of editorial and review procedures could help ensure adequate procedures to detect duplicate and fraudulent submissions.Comment: 25 pages, 12 figures, 6 table

Regulation of the co-evolved HrpR and HrpS AAA+ proteins required for Pseudomonas syringae pathogenicity.

Published versio

Early Holocene fauna from a new subfossil site: A first assessment from Christmas River, south central Madagascar

We report on faunal remains recovered during recent explorations at ‘Christmas River’, the only subfossil locality known from Madagascar’s south central plateau. Recovered remains of several extinct taxa date to approximately 10,000 14C years before present (BP), including crocodiles, tortoises, the elephant bird Aepyornis, the carnivoran Cryptoprocta spelea, the lemurs Archaeolemur majori, Pachylemur insignis, and Megaladapis edwardsi, and abundant remains of the dwarf hippopotamus, Hippopotamus lemerlei. The presence of southern - limited, forest - dependent species at Christmas River supports the hypothesis that forest once extended, perhaps discontinuously, across the central highlands towards the west. One theory is that sites in the north central highlands, which are higher in elevation, maintained more mesic conditions during Plio - Quaternary climate shifts than those of the lower elevation sites of the south central highlands. Thus, elevation above sea level may have acted as a filter that limited species dispersal across the island in the past. Such a scenario would explain the distinction between more humid, higher elevation, northern highland subfossil communities versus more arid, lower elevation, southern subfossil communities. Continued exploration at Christmas River thus provides a remarkable opportunity for deciphering ecological changes that have taken place in south central Madagascar during the Holocene.RÉSUMÉMadagascar est reconnue comme l’une des régions les plus sensibles du monde en ce qui concerne les menaces pesant sur sa biodiversité, et cela à cause de niveaux d’endémisme inégalés, d’une diversité variée et d’un impact humain important sur l’environnement. Suite à la colonisation par l’Homme il y a plus de 2000 ans, des extinctions de masse de la faune et un important recul forestier ont eu lieu en laissant des marques sur les écosystèmes modernes qui sont dans un état de bouleversement écologique. Certaines plantes endémiques, par exemple, ont perdu d’importantes espèces mutualistes, des animaux ont été obligés d’exploiter d’autres ressources ou habiter des endroits auxquels ils sont mal adaptés. La diversité des plantes et des animaux a diminué, est menacée ou a même complètement disparue de certaines routes de dissémination. Bien que l’Homme soit largement incriminé dans son rôle de déclencheur de ces extinctions massives, les transformations anthropiques qui ont contribué au changement du climat sont controversées. Les hautes - terres de Madagascar sont actuellement dominées par des zones herbeuses étendues qui agissent comme des barrières empêchant les mouvements de la faune de part et d’autre de l’île. Nous suggérons qu’une forêt humide plus ou moins continue devait s’étendre sur les hautes-terres. Des informations paléoécologiques des hautes - terres du Centre sud sontènécessaires pour évaluer cette hypothèse afin de démêler la contribution relative des facteurs climatiques et anthropiques dans les changements paléoécologiques de la région. Cependant, les stations de subfossiles étaient jusqu’alors inconnues dans cette région. Nous présentons ici les résultats de recherches réalisées sur les restes fauniques découverts au cours de fouilles récentes à Christmas River, la seule station de subfossiles connue des hautes - terres du Centre sud de Madagascar. Des restes de plusieurs espèces datant approximativement de 10,000 14C B.P. ont été identifiés dont des restes appartenant à des espèces de crocodile, de tortue, de l’Aepyornis, du carnivore Cryptoprocta spelea, des lémuriens Archaeolemur majori, Pachylemur insignis et Megaladapis edwardsi ainsi que de nombreux restes de l’hippopotame nain Hippopotamus lemerlei. La présence à Christmas River d’espèces sylvicoles endémiques du Sud appuie l’hypothèse de l’existence d’une forêt, certainement discontinue, mais qui s’étendait sur les hautes - terres centrales en se poursuivant vers l’ouest. Une théorie a proposé que les sites septentrionaux des hautes - terres centrales, à des altitudes plus élevées, maintenaient des conditions plus humides au cours des changements du Plio - quaternaire que les sites méridionaux de ces hautes - terres centrales. Ainsi, dans le passé, l’altitude a du agir comme un filtre qui empêchait la dispersion des espèces d’un endroit à l’autre de l’île. Un tel scénario expliquerait la distinction entre les communautés subfossiles du nord des hautes - terres qui étaient plus humides à haute altitude et les communautés subfossiles du sud aride à basse altitude. La poursuite de l’exploration à Christmas River constitue une occasion unique pour décoder les changements écologiques qui sont intervenus dans le Sud de cette région centrale de Madagascar au cours de l’Holocène

A mathematical and computational review of Hartree-Fock SCF methods in Quantum Chemistry

We present here a review of the fundamental topics of Hartree-Fock theory in Quantum Chemistry. From the molecular Hamiltonian, using and discussing the Born-Oppenheimer approximation, we arrive to the Hartree and Hartree-Fock equations for the electronic problem. Special emphasis is placed in the most relevant mathematical aspects of the theoretical derivation of the final equations, as well as in the results regarding the existence and uniqueness of their solutions. All Hartree-Fock versions with different spin restrictions are systematically extracted from the general case, thus providing a unifying framework. Then, the discretization of the one-electron orbitals space is reviewed and the Roothaan-Hall formalism introduced. This leads to a exposition of the basic underlying concepts related to the construction and selection of Gaussian basis sets, focusing in algorithmic efficiency issues. Finally, we close the review with a section in which the most relevant modern developments (specially those related to the design of linear-scaling methods) are commented and linked to the issues discussed. The whole work is intentionally introductory and rather self-contained, so that it may be useful for non experts that aim to use quantum chemical methods in interdisciplinary applications. Moreover, much material that is found scattered in the literature has been put together here to facilitate comprehension and to serve as a handy reference.Comment: 64 pages, 3 figures, tMPH2e.cls style file, doublesp, mathbbol and subeqn package

Lac repressor mediated DNA looping: Monte Carlo simulation of constrained DNA molecules complemented with current experimental results

Tethered particle motion (TPM) experiments can be used to detect time-resolved loop formation in a single DNA molecule by measuring changes in the length of a DNA tether. Interpretation of such experiments is greatly aided by computer simulations of DNA looping which allow one to analyze the structure of the looped DNA and estimate DNA-protein binding constants specific for the loop formation process. We here present a new Monte Carlo scheme for accurate simulation of DNA configurations subject to geometric constraints and apply this method to Lac repressor mediated DNA looping, comparing the simulation results with new experimental data obtained by the TPM technique. Our simulations, taking into account the details of attachment of DNA ends and fluctuations of the looped subsegment of the DNA, reveal the origin of the double-peaked distribution of RMS values observed by TPM experiments by showing that the average RMS value for anti-parallel loop types is smaller than that of parallel loop types. The simulations also reveal that the looping probabilities for the anti-parallel loop types are significantly higher than those of the parallel loop types, even for loops of length 600 and 900 base pairs, and that the correct proportion between the heights of the peaks in the distribution can only be attained when loops with flexible Lac repressor conformation are taken into account. Comparison of the in silico and in vitro results yields estimates for the dissociation constants characterizing the binding affinity between O1 and Oid DNA operators and the dimeric arms of the Lac repressor. © 2014 Biton et al

The Diagnostic Potential of Fe Lines Applied to Protostellar Jets

We investigate the diagnostic capabilities of iron lines for tracing the physical conditions of shock-excited gas in jets driven by pre-main sequence stars. We have analyzed the 3000-25000 \uc5, X-shooter spectra of two jets driven by the pre-main sequence stars ESO-H\u3b1 574 and Par-Lup 3-4. Both spectra are very rich in [Fe II] lines over the whole spectral range; in addition, lines from [Fe III] are detected in the ESO-H\u3b1 574 spectrum. Non-local thermal equilibrium codes solving the equations of the statistical equilibrium along with codes for the ionization equilibrium are used to derive the gas excitation conditions of electron temperature and density and fractional ionization. An estimate of the iron gas-phase abundance is provided by comparing the iron lines emissivity with that of neutral oxygen at 6300 \uc5. The [Fe II] line analysis indicates that the jet driven by ESO-H\u3b1 574 is, on average, colder (T e 3c 9000 K), less dense (n e 3c 2 7 104 cm-3), and more ionized (x e 3c 0.7) than the Par-Lup 3-4 jet (T e 3c 13,000 K, n e 3c 6 7 104 cm-3, x e < 0.4), even if the existence of a higher density component (n e 3c 2 7 105 cm-3) is probed by the [Fe III] and [Fe II] ultra-violet lines. The physical conditions derived from the iron lines are compared with shock models suggesting that the shock at work in ESO-H\u3b1 574 is faster and likely more energetic than the Par-Lup 3-4 shock. This latter feature is confirmed by the high percentage of gas-phase iron measured in ESO-H\u3b1 574 (50%-60% of its solar abundance in comparison with less than 30% in Par-Lup 3-4), which testifies that the ESO-H\u3b1 574 shock is powerful enough to partially destroy the dust present inside the jet. This work demonstrates that a multiline Fe analysis can be effectively used to probe the excitation and ionization conditions of the gas in a jet without any assumption on ionic abundances. The main limitation on the diagnostics resides in the large uncertainties of the atomic data, which, however, can be overcome through a statistical approach involving many line

Girls' disruptive behavior and its relationship to family functioning: A review

Although a number of reviews of gender differences in disruptive behavior and parental socialization exist, we extend this literature by addressing the question of differential development among girls and by placing both disruptive behavior and parenting behavior in a developmental framework. Clarifying the heterogeneity of development in girls is important for developing and optimizing gender-specific prevention and treatment programs. In the current review, we describe the unique aspects of the development of disruptive behavior in girls and explore how the gender-specific development of disruptive behavior can be explained by family linked risk and protective processes. Based on this review, we formulate a gender-specific reciprocal model of the influence of social factors on the development of disruptive behavior in girls in order to steer further research and better inform prevention and treatment programs

Honey, a Gift from Nature to Health and Beauty: A Review

Benefits of honey are contributed by the composition of its elements such as glucose, fructose, glucose oxidase, vitamins and phenolic compounds. For health, honey can be used to treat wounds due to the antibacterial activity conferred by the hydrogen peroxide produced by glucose oxidase in honey. Anti-inflammatory, anti-oxidant, deodorizing and tissue regeneration activities in honey also help in the wound healing process. It can also be an alternative sweetener for diabetic patients to ensure compliance to a healthy diet. Moreover, honey exerts several effects such as lowering low density lipids and increasing high density lipids, thus reducing risk of atherosclerosis. In terms of beauty, honey can be used on skin and hair. It moisturizes skin through its natural humectant properties contributed by high contents of fructose and glucose. Honey treats acne on the skin due to its antibacterial activity, anti-inflammatory action and tissue repair. The hair can benefit from honey in such a way that the hair has abundance, and becomes easier to comb. However, there have not been as many studies regarding the use of honey in skin in comparison to its use for health. Therefore, future studies on honey could research its use, action and benefits in both cosmetics and dermatology