Identical abnormality of the short arm of chromosome 18 in two Philadelphia-positive chronic myelocytic leukemia patients with erythroblastic transformation,resulting in duplication of BCR-ABL1 fusion

Two patients with Ph-positive chronic myelocytic leukemia in erythroblastic transformation and rearrangement of the short arm of chromosome 18 are reported. Fluorescence in situ hybridization studies showed that the 18p rearrangement resulted from translocation of the main part of chromosome 22 long arm to 18p, including BCR-ABL1 fusion. The 18p abnormality resulted, thus, in loss of 18p and duplication of BCR-ABL1 in both patients. The possible relation to the erythroblastic type of blastic phase is briefly discussed. In addition an apparently intact germline ABL1 gene was duplicated and inserted into chromosome 6 at band p21 in one of these patients.     

Autosome and Sex Chromosome Diversity Among the African Pygmy Mice, Subgenus Nannomys (Murinae; Mus)

The African pygmy mice, subgenus Nannomys, constitute the most speciose lineage of the genus Mus with 19 recognized species. Although morphologically very similar, they exhibit considerable chromosomal diversity which is here confirmed and extended by the G-banding analysis of 65 mice from West and South Africa. On the basis of their karyotype and distribution area, the specimens were assigned to at least five species. Extensive differentiation both within and between species was observed that involved almost exclusively Robertsonian translocations, 23 of which are newly described. Two of the rearrangements were sex chromosome-autosome translocations, associated in some cases with partial deletions of the X or Y chromosomes. Several authors have predicted that the highly deleterious effect of this rearrangement would be reduced if the sex and autosomal segments were insulated by a block of centromeric heterochromatin. The C-banding analyses performed showed that among the species carrying X-autosome translocations, one followed the expected pattern, while the other did not. In this case, functional isolation of the sex and autosome compartments must involve other repetitive sequences or genomic traits that require further molecular characterization. Such studies will provide insight into the causes and consequences of the high diversity of sex chromosome rearrangements in this subgenus.     

Human TLR-7-, -8-, and -9-mediated induction of IFN-alpha/beta and -lambda Is IRAK-4 dependent and redundant for protective immunity to viruses

Five TLRs are thought to play an important role in antiviral immunity, sensing viral products and inducing IFN-alpha/beta and -lambda. Surprisingly, patients with a defect of IRAK-4, a critical kinase downstream from TLRs, are resistant to common viruses. We show here that IFN-alpha/beta and -lambda induction via TLR-7, TLR-8, and TLR-9 was abolished in IRAK-4-deficient blood cells. In contrast, IFN-alpha/beta and -lambda were induced normally by TLR-3 and TLR-4 agonists. Moreover, IFN-beta and -lambda were normally induced by TLR-3 agonists and viruses in IRAK-4-deficient fibroblasts. We further show that IFN-alpha/beta and -lambda production in response to 9 of 11 viruses tested was normal or weakly affected in IRAK-4-deficient blood cells. Thus, IRAK-4-deficient patients may control viral infections by TLR-3- and TLR-4-dependent and/or TLR-independent production of IFNs. The TLR-7-, TLR-8-, and TLR-9-dependent induction of IFN-alpha/beta and -lambda is strictly IRAK-4 dependent and paradoxically redundant for protective immunity to most viruses in humans.     

Dynamic balance of metabotropic inputs causes dorsal horn neurons to switch functional states

Sensory relay structures in the spinal cord dorsal horn are now thought to be active processing structures that function before supraspinal sensory integration. Dorsal horn neurons directly receive nociceptive (pain) signals from the periphery, express a high degree of functional plasticity and are involved in long-term sensitization and chronic pain. We show here that deep dorsal horn neurons (DHNs) in Wistar rats can switch their intrinsic firing properties from tonic to plateau or endogenous bursting patterns, depending upon the balance of control by metabotropic glutamate (mGlu) and GABA(B) receptors. We further show that this modulation acts on at least one common target, the inwardly rectifying potassium channel (Kir3). Finally, we found that these firing modes correspond to specific functional states of information transfer in which dorsal horn neurons can faithfully transmit, greatly enhance or block the transfer of nociceptive information.     

Genetic variation in locomotor activity rhythm among populations ofLeptopilina heterotoma (Hymenoptera: Eucoilidae), a larval parasitoid ofDrosophila species

The locomotor activity rhythm ofLeptopilina heterotoma, a parasitoid insect ofDrosophila larvae, was investigated under laboratory conditions. Under LD 1212, the locomotor activity of females shows a clear rhythm which persists under continuous darkness (circadian rhythm). However, comparative study of five populations indicates that both the rate of activity and the profile of the rhythm vary according to the origin of females. The Mediterranean populations (Tunisia and Antibes) show two peaks of activity, at the beginning and at the end of the photophase, whereas more northern populations (Lyon and the Netherlands) are mostly active during the afternoon. Females originating from the area of Lyon have a very low level of activity. Reciprocal crosses (F₁ hybrids and backcrosses) between the French and the Tunisian strains demonstrated the genetic basis of these variations and the biparental inheritance of the trait. This genetic variability is interpreted as a consequence of selective pressures and suggests a local adaptation of natural populations in host foraging behavior. The selective factors which could act on the daily organization of parasitoid behaviors are discussed.     

High-intensity intermittent running training improves pulmonary function and alters exercise breathing pattern in children

We investigated the effects of short duration running training on resting and exercise lung function in healthy prepubescent children. One trained group (TrG) (n = 9; three girls and six boys; age = 9.7 ± 0.9 year) participated in 8 weeks of high-intensity intermittent running training and was compared to a control group (ContG) (n = 9; four girls and five boys; age = 10.3 ± 0.7 year). Before and after the 8-week period, the children performed pulmonary function tests and an incremental exercise test on a cycle ergometer. After the 8-week period, no change was found in pulmonary function in ContG. Conversely, an increase in forced vital capacity (FVC) (+7 ± 4% ; P = 0.026), forced expiratory volume in one second (+11 ± 6% ; P = 0.025), peak expiratory flows (+17 ± 4% ; P = 0.005), maximal expiratory flows at 50% (+16 ± 10% ; P = 0.019) and 75% (+15 ± 8% ; P = 0.006) of FVC were reported in TrG. At peak exercise, TrG displayed higher values of peak oxygen consumption (+15 ± 4% ; P<0.001), minute ventilation (+16 ± 5% ; P = 0.033) and tidal volume (+15 ± 5% ; P = 0.019) after training. At sub-maximal exercise, ventilatory response to exercise was lower (P = 0.017) in TrG after training, associated with reduced end-tidal partial oxygen pressure (P<0.05) and higher end-tidal partial carbon dioxide pressure (P = 0.026). Lower deadspace volume relative to tidal volume was found at each stage of exercise in TrG after training (P<0.05). Eight weeks of high-intensity intermittent running training enhanced resting pulmonary function and led to deeper exercise ventilation reflecting a better effectiveness in prepubescent children.