Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

Background: Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods: Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results: We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients' samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions: These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current "wait and see approach" in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits

Macrocheles bertrandi Niogret & Nicot, 2008, sp. nov.

Macrocheles bertrandi sp. nov. Type series. Holotype: Female, Gabon, Bakoumba, 1 ° 79 ' S, 13 ° 04' E, equatorial climate, June 2006, 623 m alt., on Stomoxys calcitrans. Paratypes: 3 females, same data as holotype, deposited in collection of the Muséum National d’Histoire Naturelle de Paris, France; 2 females, same data as holotype, deposited in the collection of the Laboratoire de Zoogéographie, University of Montpellier, France. Female. Yellowish colour, medium size. Dorsal shield (Fig. 2 a). Shield elongated, similar to M. robustulus in shape; longer than wide; length 591 ± 45 µm, width 319 ± 14 µm (n = 6), with distinct ornamentation underlined by punctures, divided by the procurved line at level of setae s 5; reticular pattern irregular with pentagons or hexagons; shield with 28 pairs of setae; j 1 directed forward and weakly pilose distally; z 1 smooth, reduced in length; all other setae simple, except J 5 serrated for it whole length. Ve n t r a l idiosoma (Fig. 2 b). Tritosternum and peritremes normal for genus. Sternal shield longer than wide; length 148 ± 7 µm, width 103 ± 9 µm (n = 6); with three pairs of smooth setae and two pairs of pores. Weak ornamentation underlined by punctures; discrete linea media transversa underlined by some bigger punctures; oblique anterior lines and arched line not visible; punctate angular lines similar to those of M. muscaedomesticae group; posterior half of sternal shield with indeterminate area punctata, irregular and sparse large punctures between st 3. Epigynial shield longer than wide; 98-100 µm long, 96-98 µm wide; with a pair of setae; shield weakly ornamented, sclerotized lines forming three arched patterns underlined by punctures, two of them cross a central ovoid shape formed by punctures. Ventri-anal shield longer than wide (ca. 166- 170 µm long); with eight main transverse punctured curved lines, longitudinal lines and lateral weak ornamentations; with three pairs of pre anal setae, a pair of para-anal setae and a post-anal seta. Metasternal plates elongated with a pore and a simple setae. Gnathosoma. Typical for the M. glaber -group. Chelicerae robust (Fig. 2 c) with well developed median tooth, pyramidal in shape and a terminal hook, pilus dentilis straight; movable digit with two teeth; arthrodial brush reaching mid length of movable digit. Hypostomal groove with five transverse rows of denticles. Epistome with a pair of broad lateral elements, tapering distally, median element thinner and shorter, forked distally. Sacculus foeminus M. glaber -like. Legs. Setae simple or lightly pilose at the distal end, except setae on genu I, tibia and basitarsus IV and tarsi long and thin. Genu IV with 6 simple setae, leg IV chaetotaxy typical for the genus. Etymology. The species is dedicated to Dr. Michel Bertrand, Acarologist, University of Montpellier (France).Published as part of Niogret, Jerome & Nicot, Antoine, 2008, Combined approach using morphology and ITS-sequences for description of three new species of Macrocheles (Acari: Macrochelidae), pp. 39-49 in Zootaxa 1873 on pages 43-44, DOI: 10.5281/zenodo.18403

Data from: Timing malaria transmission with mosquito fluctuations

Temporal variations in the activity of arthropod vectors can dramatically affect the epidemiology and evolution of vector-borne pathogens. Here we explore the “Hawking hypothesis” stating that these pathogens may evolve the ability to time investment in transmission to match the activity of their vectors. First, we use a theoretical model to identify the conditions promoting the evolution of time-varying transmission strategies in pathogens. Second, we experimentally test the “Hawking hypothesis” by monitoring the within-host dynamics of Plasmodium relictum throughout the acute and the chronic phases of the bird infection. We detect a periodic increase of parasitaemia and mosquito infection in the late afternoon that coincides with an increase in the biting activity of its natural vector. We also detect a positive effect of mosquito bites on Plasmodium replication in the birds both in the acute and in the chronic phases of the infection. This study highlights that Plasmodium parasites use two different strategies to increase the match between transmission potential and vector availability. We discuss the adaptive nature of these unconditional and plastic transmission strategies with respect to the time-scale and the predictability of the fluctuations in the activity of the vector

Macrocheles ovoidalis Niogret & Nicot, 2008, sp. nov.

<i>Macrocheles ovoidalis</i> sp. nov. <p> <b>Type series. Holotype: Female,</b> Gabon, Bakoumba, 1° 79' S, 13° 04' E, equatorial climate, June 2006, 623 m alt., on <i>Stomoxys calcitrans</i>. Paratypes: 3 females, same data as for holotype, deposited in collections of the Muséum National d’Histoire Naturelle de Paris (France); other paratypes (2 females) same data as for holotype, deposited in the collection of the Laboratoire de Zoogéographie, University of Montpellier, France.</p> <p> <b>Female</b>. Brown in colour, medium size.</p> <p> <i>Dorsal shield</i> (Fig. 3 a). Shield rounded, longer than wide; length 488 ± 53 µm, width 280 ± 8 µm (n = 6); with distinct ornamentation, punctured procurved line, reticular pattern of irregular pentagons or hexagons heavily covered by punctures; polygons less visible in median zone. Shield with 28 pairs of setae; <i>j1</i> directed forward, expanded and pilose in distal half; <i>z1</i> smooth, reduced in length; setae <i>j2-6</i>, <i>z1</i>, z5, <i>z6</i>, <i>s1</i>, <i>J2</i> and <i>J5</i> simple; <i>S4</i>, <i>S5</i> and <i>Z4</i> pilose in distal third; <i>Z5</i> weakly pilose in distal third; other setae distally pilose.</p> <p> <i>Ve n t r a l idiosoma</i> (Fig. 3 b). Tritosternum and peritremes normal for genus. Sternal shield slightly longer than wide; length 104 ± 10 µm, width at level of coxae II 98 ± 4 µm (n = 6); with three pairs of smooth setae and two pairs of elongated pores. Strong globular ornamentations aggregated and forming symmetrical grapelike pattern (19 polygons per side); anterior margin (around first setal insertion) and posterior margin lacking in such an ornamental pattern, with only sparse punctations. Median transverse line, oblique anterior lines, angular line and arched line not visible. Epigynial shield wider than long; 168-171 µm long, 193-197 µm wide; with a pair of setae; shield with strong ornamentation, with several backward-directed arched lines forming a tile-like pattern; four median arched lines crossed by four other arched lines on each side of the shield. Ventri-anal shield wider than long, 74-77 µm long, 111-115 µm wide, covered by dense globular tiles similar to epigynial shield, with eight main clearly visible backward-directled transverse curved lines. Longitudinal and curved lines delimit rectangles covered by globular tiles; with three pairs of pre-anal setae, a pair of para-anal setae and a post-anal seta. Metasternal plates elongate, oval, with a pore and a simple seta.</p> <p> <i>Gnathosoma</i>. Typical for the <i>M</i>. <i>glaber</i> -group. Chelicerae robust (Fig. 3 c) <i>pilus dentilis</i> straight; arthrodial brush reaching mid length of movable digit, movable digit with one tooth. Palpi similar to <i>M</i>. <i>glaber</i>. Epistome <i>glaber</i> -like in shape, with smooth lateral lobes and long and pilose central branches. <i>Legs</i>. Setae simple or lightly pilose at the distal end except setae on genu I, tibia and basitarsus IV and tarsi, setae long and thin.</p> <p> <i>Etymology</i>. The specific name refers to the ovoid body shape of the species.</p>Published as part of <i>Niogret, Jerome & Nicot, Antoine, 2008, Combined approach using morphology and ITS-sequences for description of three new species of Macrocheles (Acari: Macrochelidae), pp. 39-49 in Zootaxa 1873</i> on pages 44-45, DOI: <a href="http://zenodo.org/record/184031">10.5281/zenodo.184031</a&gt

Macrocheles lumareti Niogret & Nicot, 2008, sp. nov

<i>Macrocheles lumareti</i> sp. nov <p> <i>Material examined.</i> <b>Holotype: Female</b>, France, St Germain-Les-Buxy, France, 46° 42' N, 4° 46' E, May 2006, 206 m alt., on body of <i>Copris lunaris</i>. Paratypes: 3 females, same data as holotype, deposited in collections of the Muséum National d’Histoire Naturelle de Paris, France; 2 females, same data as holotype, deposited in the collections of the Laboratoire de Zoogéographie, University of Montpellier, France.</p> <p> <b>Female</b>. Yellowish-brown in colour, medium size.</p> <p> <i>Dorsal shield</i> (Fig. 1 a). Shield similar to <i>M</i>. <i>glaber</i> in shape, longer than wide, with procurved line underlined by punctured lines; length 808 ± 91 µm, width 444 ± 34 µm (n = 6); reticular pattern underlined by punctures with large and irregular pentagons or hexagons; reticular pattern weaker in regular curved lines around setae <i>J2</i>; two distinct small cracks close to setae <i>j6</i>. Shield with 28 pairs of setae; <i>j1</i> pilose and directed forward; <i>z1</i> smooth, reduced in length; setae <i>j4</i>, <i>z2</i>, <i>z4</i>, and <i>r2-4</i> pilose and <i>j2</i>, <i>j3</i>, and <i>s4</i> distally pilose; <i>J5</i> serrated for its whole length; <i>Z5</i> and <i>S5</i> barbed.</p> <p> <i>Ve n tr al idiosoma</i> (Fig. 1 b). Tritosternum and peritremes normal for the genus. Sternal shield rather large, length 160 ± 4 µm, width at level of coxae II 156 ± 1 µm (n = 6); with three pairs of smooth setae and two pairs of pores; surface ornamented with weak relief unmarked by punctures, a discrete <i>linea media transversa</i>; pair of <i>linea oblique anteriores</i> weakly visible; part of <i>linea angulata</i>, two lateral ridges and one <i>linea arcuata</i> forming a first rectangle; posterior <i>linea arcuata</i>, part of <i>linea media transversa</i> and two lateral ridges forming another quadrangular shape. Posterior part of sternal shield with sparse and irregular weak punctures; <i>area punctiformes</i> not visible and <i>area punctata posteriores</i> undelimited. Epigynial shield wider than long; 110- 114 µm long, 145-165 µm wide; with a pair of setae. Epigynial shield with sclerotization attenuated anteriorly; sclerotized lines forming two arched patterns underlined by punctures, without other visible ornamental pattern. Ventri-anal shield as wide as long (<i>ca</i>. 258 µm long), with seven semiconcentric lines underlined by weak reticulations; longitudinal and lateral ornamentations obscure; with three pairs of pre-anal setae, a pair of para-anal setae and a post-anal seta. Metasternal plates elongate, with a pore and a simple seta.</p> <p> <i>Gnathosoma</i>. Typical of the <i>M</i>. <i>glaber</i> -group. Chelicerae (Fig. 1 c) robust with well developed median tooth, pyramidal in shape; <i>pilus dentilis</i> straight; movable digit with a large tooth and one smaller tooth; arthrodial brush reaching mid length of movable digit; hypostomal groove with five transverse rows of denticles. Palp similar to that of <i>M</i>. <i>glaber</i>. Epistome <i>glaber</i> -like in shape with smooth lateral lobes and pilose central branch (Fig. 1 d).</p> <p> <i>Spermatheca</i>. Sacculus wide, elongate (45 µm width); sperm ducts open in the lateral vesicles (spherical lobes) with large tubular section; corniculus long (<i>ca</i>. 50 µm), median sacculus rounded, pear-shaped. <i>Legs</i>. Setae simple or lightly pilose at the distal end except setae on genu I, tibia and basitarsus IV; tarsi with long thin setae. Genu IV with 6 simple setae.</p> <p> <i>Etymology</i>. The species is dedicated to Professor Jean-Pierre Lumaret, University of Montpellier (France).</p>Published as part of <i>Niogret, Jerome & Nicot, Antoine, 2008, Combined approach using morphology and ITS-sequences for description of three new species of Macrocheles (Acari: Macrochelidae), pp. 39-49 in Zootaxa 1873</i> on pages 41-42, DOI: <a href="http://zenodo.org/record/184031">10.5281/zenodo.184031</a&gt

Energetic cost of insecticide resistance in Culex pipiens mosquitoes

The extensive use of insecticides to control vector populations has lead to the widespread development of different mechanisms of insecticide resistance. Mutations that confer insecticide resistance are often associated to fitness costs that prevent them from spreading to fixation. In vectors, such fitness costs include reductions in preimaginal survival, adult size, longevity, and fecundity. The most commonly invoked explanation for the nature of such pleiotropic effects of insecticide resistance is the existence of resource-based trade-offs. According to this hypothesis, insecticide resistance would deplete the energetic stores of vectors, reducing the energy available for other biological functions and generating trade-offs between insecticide resistance and key life history traits. Here we test this hypothesis by quantifying the energetic resources (lipids, glycogen, and glucose) of larvae and adult females of the mosquito Culex pipiens L. resistant to insecticides through two different mechanisms: esterase overproduction and acetylcholinesterase modification. We find that, as expected from trade-off theory, insecticide resistant mosquitoes through the overproduction of esterases contain on average 30% less energetic reserves than their susceptible counterparts. Acetylcholinesterase-modified mosquitoes, however, also showed a significant reduction in energetic resources (20% less). We suggest that, in acetylcholinesterase-modified mosquitoes, resource depletion may not be the result of resource-based trade-offs but a consequence of the hyperactivation of the nervous system. We argue that these results not only provide a mechanistic explanation for the negative pleiotropic effects of insecticide resistance on mosquito life history traits but also can have a direct effect on the development of parasites that depend on the vector's energetic reserves to fulfil their own metabolic needs

Mesoscale investigation of fine grain contribution to contact stress in granular materials

International audienceFine grains play an important role in mechanical properties of granular materials as they control how plastic strain may develop, which has a noticeable impact on mechanical stability. In this work, we use numerical simulations based on a discrete element method (DEM) to analyze the stress contribution of fine grains to the total stress. Different from usual DEM simulations, the analysis is conducted directly at the mesoscopic scale by considering an idealized grain assembly. The results show how fine grains get progressively jammed and increasingly participate to stress transmission. Fine contribution to contact stress is shown to be non-isotropic. The principal anisotropy direction coincides with the principal direction of contraction and the anisotropy ratio (i.e. the ratio between the largest and the smallest eigenvalues of the fine stress) is shown to be limited (⁄ ≃ 2). By performing strain controlled directional analyses, an analytical model is proposed to account for the stress contribution of fine grains along various loading paths. Its simple form will help to enrich advanced micro-mechanically-based constitutive formulations, and better account for the constitutive behavior of widely graded granular materials