Journals
2012 EN
Elizabeth A. Becker · Sarah K. Petruno · Catherine A. Marler
Scent marking can provide behavioral and physiological information including territory ownership and mate advertisement. It is unknown how mating status and pair cohabitation influence marking by males from different social systems. We compared the highly territorial and monogamous California mouse ( Peromyscus californicus ) to the less territorial and promiscuous white-footed mouse ( P. leucopus ). Single and mated males of both species were assigned to one of the following arenas lined with filter paper: control (unscented arena), male scented (previously scent-marked by a male conspecific), or females present (containing females in small cages). As expected, the territorial P. californicus scent marked and overmarked an unfamiliar male conspecific's scent marks more frequently than P. leucopus . Species differences in responses to novel females were also found based on mating status. The presence of unfamiliar females failed to induce changes in scent marking in pair bonded P. californicus even though virgin males increased marking behavior. Pair bonding appears to reduce male advertisement for novel females. This is in contrast to P. leucopus males that continue to advertise regardless of mating status. Our data suggest that communication through scent-marking can diverge significantly between species based on mating system and that there are physiological mechanisms that can inhibit responsiveness of males to female cues.
Public Library of Science
Journals
2012 EN
Julie H. Levison · Catherine Orrell · Sébastien Gallien
+5 more
Background We investigated the prevalence of wild-type virus (no major drug resistance) and drug resistance mutations at second-line antiretroviral treatment (ART) failure in a large HIV treatment program in South Africa. Methodology/ Principal Findings HIV-infected patients ≥15 years of age who had failed protease inhibitor (PI)-based second-line ART (2 consecutive HIV RNA tests >1000 copies/ml on lopinavir/ritonavir, didanosine, and zidovudine) were identified retrospectively. Patients with virologic failure were continued on second-line ART. Genotypic testing for drug resistance was performed on frozen plasma samples obtained closest to and after the date of laboratory confirmed second-line ART failure. Of 322 HIV-infected patients on second-line ART, 43 were adults with confirmed virologic failure, and 33 had available plasma for viral sequencing. HIV-1 RNA subtype C predominated (n = 32, 97%). Mean duration on ART (SD) prior to initiation of second-line ART was 23 (17) months, and time from second-line ART initiation to failure was 10 (9) months. Plasma samples were obtained 7(9) months from confirmed failure. At second-line failure, 22 patients (67%) had wild-type virus. There was no major resistance to PIs found. Eleven of 33 patients had a second plasma sample taken 8 (5.5) months after the first. Median HIV-1 RNA and the genotypic resistance profile were unchanged. Conclusions/ Significance Most patients who failed second-line ART had wild-type virus. We did not observe evolution of resistance despite continuation of PI-based ART after failure. Interventions that successfully improve adherence could allow patients to continue to benefit from second-line ART therapy even after initial failure.
Public Library of Science
Journals
2012 EN
Cyrille Mathieu · Vanessa Guillaume · Amélie Sabine
+4 more
Nipah virus (NiV) is a recently emerged zoonotic Paramyxovirus that causes regular outbreaks in East Asia with mortality rate exceeding 75%. Major cellular targets of NiV infection are endothelial cells and neurons. To better understand virus-host interaction, we analyzed the transcriptome profile of NiV infection in primary human umbilical vein endothelial cells. We further assessed some of the obtained results by in vitro and in vivo methods in a hamster model and in brain samples from NiV-infected patients. We found that NiV infection strongly induces genes involved in interferon response in endothelial cells. Among the top ten upregulated genes, we identified the chemokine CXCL10 (interferon-induced protein 10, IP-10), an important chemoattractant involved in the generation of inflammatory immune response and neurotoxicity. In NiV-infected hamsters, which develop pathology similar to what is seen in humans, expression of CXCL10 mRNA was induced in different organs with kinetics that followed NiV replication. Finally, we showed intense staining for CXCL10 in the brain of patients who succumbed to lethal NiV infection during the outbreak in Malaysia, confirming induction of this chemokine in fatal human infections. This study sheds new light on NiV pathogenesis, indicating the role of CXCL10 during the course of infection and suggests that this chemokine may serve as a potential new marker for lethal NiV encephalitis.
Public Library of Science
Journals
2012 EN
Nicolas Kalfa · Maki Fukami · Pascal Philibert
+8 more
More than 50% of children with severe 46,XY disorders of sex development (DSD) do not have a definitive etiological diagnosis. Besides gonadal dysgenesis, defects in androgen biosynthesis, and abnormalities in androgen sensitivity, the Mastermind-like domain containing 1 ( MAMLD1 ) gene, which was identified as critical for the development of male genitalia, may be implicated. The present study investigated whether MAMLD1 is implicated in cases of severe 46,XY DSD and whether routine sequencing of MAMLD1 should be performed in these patients. Seventy children with severe non-syndromic 46,XY DSD of unknown etiology were studied. One hundred and fifty healthy individuals were included as controls. Direct sequencing of the MAMLD1, AR, SRD5A2 and NR5A1 genes was performed. The transactivation function of the variant MAMLD1 proteins was quantified by the luciferase method. Two new mutations were identified: p.S143X (c.428C>A) in a patient with scrotal hypospadias with microphallus and p.P384L (c.1151C>T) in a patient with penile hypospadias with microphallus. The in vitro functional study confirmed no residual transactivating function of the p.S143X mutant and a significantly reduced transactivation function of the p.P384L protein ( p = 0.0032). The p.P359S, p.N662S and p.H347Q variants are also reported with particularly high frequency of the p.359T- p.662G haplotype in the DSD patients. Severe undervirilization in XY newborns can reveal mutations of MAMLD1. MAMLD1 should be routinely sequenced in these patients with otherwise normal AR, SRD5A2 and NR5A1 genes.
Public Library of Science
Journals
2012 EN
Catherine Kielar · Stephen J. Sawiak · Paloma Navarro Negredo
+2 more
Complexins (Cplxs) are small, soluble, regulatory proteins that bind reversibly to the SNARE complex and modulate synaptic vesicle release. Cplx1 knockout mice ( Cplx1 −/− ) have the earliest known onset of ataxia seen in a mouse model, although hitherto no histopathology has been described in these mice. Nevertheless, the profound neurological phenotype displayed by Cplx1 −/− mutants suggests that significant functional abnormalities must be present in these animals. In this study, MRI was used to automatically detect regions where structural differences were not obvious when using a traditional histological approach. Tensor-based morphometry of Cplx1 −/− mouse brains showed selective volume loss from the thalamus and cerebellum. Stereological analysis of Cplx1 −/− and Cplx1 +/+ mice brain slices confirmed the volume loss in the thalamus as well as loss in some lobules of the cerebellum. Finally, stereology was used to show that there was loss of cerebellar granule cells in Cplx1 −/− mice when compared to Cplx1 +/+ animals. Our study is the first to describe pathological changes in Cplx1 −/− mouse brain. We suggest that the ataxia in Cplx1 −/− mice is likely to be due to pathological changes in both cerebellum and thalamus. Reduced levels of Cplx proteins have been reported in brains of patients with neurodegenerative diseases. Therefore, understanding the effects of Cplx depletion in brains from Cplx1 −/− mice may also shed light on the mechanisms underlying pathophysiology in disorders in which loss of Cplx1 occurs.
Public Library of Science
Journals
2012 EN
Rana W. ElSabaawi · Tyler J. Kohler · Eugênia Zandonà
+8 more
The elemental composition of animals, or their organismal stoichiometry, is thought to constrain their contribution to nutrient recycling, their interactions with other animals, and their demographic rates. Factors that affect organismal stoichiometry are generally poorly understood, but likely reflect elemental investments in morphological features and life history traits, acting in concert with the environmental availability of elements. We assessed the relative contribution of organismal traits and environmental variability to the stoichiometry of an insectivorous Neotropical stream fish, Rivulus hartii . We characterized the influence of body size, life history phenotype, stage of maturity, and environmental variability on organismal stoichiometry in 6 streams that differ in a broad suite of environmental variables. The elemental composition of R. hartii was variable, and overlapped with the wide range of elemental composition documented across freshwater fish taxa. Average %P composition was ∼3.2%(±0.6), average %N∼10.7%(±0.9), and average %C∼41.7%(±3.1). Streams were the strongest predictor of organismal stoichiometry, and explained up to 18% of the overall variance. This effect appeared to be largely explained by variability in quality of basal resources such as epilithon N∶P and benthic organic matter C∶N, along with variability in invertebrate standing stocks, an important food source for R. hartii . Organismal traits were weak predictors of organismal stoichiometry in this species, explaining when combined up to 7% of the overall variance in stoichiometry. Body size was significantly and positively correlated with %P, and negatively with N∶P, and C∶P, and life history phenotype was significantly correlated with %C, %P, C∶P and C∶N. Our study suggests that spatial variability in elemental availability is more strongly correlated with organismal stoichiometry than organismal traits, and suggests that the stoichiometry of carnivores may not be completely buffered from environmental variability. We discuss the relevance of these findings to ecological stoichiometry theory.
Public Library of Science
Journals
2012 EN
Hyunchul Lee · Catherine A. Leamey · Atomu Sawatari
The striatum is the primary input nucleus of the basal ganglia, a collection of nuclei that play important roles in motor control and associative learning. We have previously reported that perineuronal nets (PNNs), aggregations of chondroitin-sulfate proteoglycans (CSPGs), form in the matrix compartment of the mouse striatum during the second postnatal week. This period overlaps with important developmental changes, including the attainment of an adult-like gait. Here, we investigate the identity of the cells encapsulated by PNNs, characterize their topographical distribution and determine their function by assessing the impact of enzymatic digestion of PNNs on two striatum-dependent behaviors: ambulation and goal-directed spatial learning. We show PNNs are more numerous caudally, and that a substantial fraction (41%) of these structures surrounds parvalbumin positive (PV+) interneurons, while approximately 51% of PV+ cells are ensheathed by PNNs. The colocalization of these structures is greatest in dorsal, lateral and caudal regions of the striatum. Bilateral digestion of striatal PNNs led to an increase in both the width and variability of hind limb gait. Intriguingly, this also resulted in an improvement in the acquisition rate of the Morris water maze. Together, these data show that PNNs are associated with specific elements of striatal circuits and play a key role in regulating the function of this important structure in the mouse.
Public Library of Science
Journals
2012 EN
Anne-Catherine Schneider · Pauline Béguin · Sophie Bourez
+5 more
Background Conjugated linoleic acids (CLA), and principally c9t11 CLA, are suspected to have numerous preventive properties regarding non-infectious pathologies such as inflammatory diseases, atherosclerosis and several types of cancer. C9t11 CLA is produced in the rumen during biohydrogenation of linoleic acid, but can also be synthesized in mammalian tissues from trans -vaccenic acid (C18:1 t11) through the action of delta-9 desaturase (D9D). For several years, it is also known that c9t11 CLA can be synthesized from conjugated linolenic acids (CLnA), i.e. c9t11c13 CLnA and c9t11t13 CLnA. This study aimed at investigating to which extent and by which route c9t11 CLA can be produced from another isomer of CLA, the t11t13 CLA that is structurally very similar to c9t11t13 CLnA, in Caco-2 cells. Methodology/Principal Findings Caco-2 cells were incubated for 24 h with 20 µmol/l of t11t13 CLA in the absence or presence of sterculic oil used as an inhibitor of D9D. Caco-2 cells were able to convert t11t13 CLA into c9t11 CLA, and c9t11t13 CLnA was formed as an intermediate compound. In the presence of sterculic oil, the production of this intermediate was decreased by 46% and the formation of c9t11 CLA was decreased by 26%. No other metabolite was detected. Conclusions/Significance These results not only highlight the conversion of t11t13 CLA into c9t11 CLA but demonstrate also that this conversion involves first a desaturation step catalysed by D9D to produce c9t11t13 CLnA and then the action of another enzyme reducing the double bond on the Δ13 position.
Public Library of Science
Journals
2012 EN
Catherine Pitt · Halimatou Diawara · Dimlawendé J. Ouédraogo
+10 more
Background Intermittent preventive treatment of malaria in children (IPTc) is a highly efficacious method of malaria control where malaria transmission is highly seasonal. However, no studies published to date have examined community perceptions of IPTc. Methods A qualitative study was undertaken in parallel with a double-blind, placebo-controlled, randomized trial of IPTc conducted in Mali and Burkina Faso in 2008–2009 to assess community perceptions of and recommendations for IPTc. Caregivers and community health workers (CHWs) were purposively sampled. Seventy-two in-depth individual interviews and 23 focus group discussions were conducted. Findings Widespread perceptions of health benefits for children led to enthusiasm for the trial and for IPTc specifically. Trust in and respect for those providing the tablets and a sense of obligation to the community to participate in sanctioned activities favoured initial adoption. IPTc fits in well with existing understandings of childhood illness. Participants did not express concerns about the specific drugs used for IPTc or about providing tablets to children without symptoms of malaria. There was no evidence that IPTc was perceived as a substitute for bed net usage, nor did it inhibit care seeking. Participants recommended that distribution be “closer to the population”, but expressed concern over caregivers' ability to administer tablets at home. Conclusions The trial context mediated perceptions of IPTc. Nonetheless, the results indicate that community perceptions of IPTc in the settings studied were largely favourable and that the delivery strategy rather than the tablets themselves presented the main areas of concern for caregivers and CHWs. The study identifies a number of key questions to consider in planning an IPTc distribution strategy. Single-dose formulations could increase the success of IPTc implementation, as could integration of IPTc within a package of activities, such as bed net distribution and free curative care, for which demand is already high.
Public Library of Science
Journals
2012 EN
Hédia Chagraoui · Catherine Porcher
Because of the scarcity of megakaryocytes in hematopoietic tissues, studying megakaryopoiesis heavily relies on the availability of appropriate cellular models. Here, we report the establishment of a new mouse embryonic stem (ES) cell-derived megakaryocytic cell line, MKD1. The cells are factor-dependent, their cell surface immunophenotype and gene expression profile closely resemble that of primary megakaryocyte progenitors (MkPs) and they further differentiate along the megakaryocyte lineage upon valproic acid treatment. At a functional level, we show that ablation of SCL expression, a transcription factor critical for MkP maturation, leads to gene expression alterations similar to that observed in primary, Scl-excised MkPs. Moreover, the cell line is amenable to biochemical and transcriptional analyses, as we report for GpVI , a direct target of SCL. Thus, the MKD1 cell line offers a pertinent experimental model to study the cellular and molecular mechanisms underlying MkP biology and more broadly megakaryopoiesis.
Public Library of Science