Mother’s scent for motherless neonates: Responses of artificially reared lambs to ewe’s inguinal wax odor

International audienceMammalian newborns depend on their mother’s milk to satisfy their initial needs of protection and nutrition. They reach the source of milk in following visual, tactile and olfactory cues. In particular, parturient ewes produce an odorous wax in the inguinal glands close to the teats. When presented separately to newly born lambs, this inguinal wax (IW) elicits arousal, head orientation, licking and increased respiratory rate indicative of their avidity for it. The present study assessed whether transferring IW into the environment of artificially fed lambs would improve their responses to the novelty of the situation. We first assessed whether suckled lambs preferred an IW-scented teat to a scentless control teat. Then, we assessed whether a teat odorized with IW was more easily learned as suckable relative to a control teat. Finally, the lambs’ growth performance from postnatal days (PND) 0 and 20 was compared in groups reared with or without IW spread on the milk-feeder in their home pen. The behavioral assays did not evidence any significant effect of IW odor on previously suckled lambs’ attraction and appetence responses. However, relative to the scentless control condition, being exposed to an IW-smeared milk-feeder led to a higher body weight at 20 days after birth. In the conditions of the present study, namely after suckling initiation, IW odor appeared not to be a strong determinant of short-term attraction or appetitive behavior in neonate lambs. The continued presence of IW, a familiar odor, in the artificial suckling context may improve artificially-reared lambs’ emotional state that may affect their weight gain

Alcohol use, mycoplasma genitalium, and other STIs associated With HIV incidence among women at high risk in Kampala, Uganda.

BACKGROUND: In 2008, the first clinic for women involved in high-risk sexual behavior was established in Kampala, offering targeted HIV prevention. This article describes rates, determinants, and trends of HIV incidence over 3 years. METHODS: A total of 1027 women at high risk were enrolled into a closed cohort. At 3-monthly visits, data were collected on sociodemographic variables and risk behavior; biological samples were tested for HIV and other reproductive tract infections/sexually transmitted infections (RTI/STIs). Hazard ratios for HIV incidence were estimated using Cox proportional hazards regression among the 646 women HIV negative at enrolment. RESULTS: HIV incidence was 3.66/100 person-years (pyr) and declined from 6.80/100 pyr in the first calendar year to 2.24/100 pyr and 2.53/100 pyr in the following years (P trend = 0.003). Sociodemographic and behavioral factors independently associated with HIV incidence were younger age, younger age at first sex, alcohol use (including frequency of use and binge drinking), number of paying clients in the past month, inconsistent condom use with clients, and not being pregnant. HIV incidence was also independently associated with Mycoplasma genitalium infection at enrolment [adjusted hazard ratio (aHR) = 2.28, 95% confidence interval (CI): 1.15 to 4.52] and with Neisseria gonorrhoeae (aHR = 5.91, 95% CI: 3.04 to 11.49) and Trichomonas vaginalis infections at the most recent visit (aHR = 2.72, 95% CI: 1.27 to 5.84). The population attributable fractions of HIV incidence for alcohol use was 63.5% (95% CI: 6.5 to 85.8) and for treatable RTI/STIs was 70.0% (95% CI: 18.8 to 87.5). CONCLUSIONS: Alcohol use and STIs remain important risk factors for HIV acquisition, which call for more intensive control measures in women at high risk. Further longitudinal studies are needed to confirm the association between M. genitalium and HIV acquisition

Varia

Le numéro 19 de la Revue de la régulation marque l’entrée de la revue dans sa 10e année, qui fait suite, rappelons-le, à L’Année de la régulation qui a paru régulièrement de 1997 à 2008. Ce numéro porte notamment le sceau du colloque « La théorie de la régulation à l’épreuve des crises », qui en juin 2015 a dressé le bilan et présenté les perspectives de la théorie à l’occasion des 40 ans de la parution des textes fondateurs

RAS activation induces synthetic lethality of MEK inhibition with mitochondrial oxidative metabolism in acute myeloid leukemia

International audienceDespite recent advances in acute myeloid leukemia (AML) molecular characterization and targeted therapies, a majority of AML cases still lack therapeutically actionable targets. In 127 AML cases with unmet therapeutic needs, as defined by the exclusion of ELN favorable cases and of FLT3-ITD mutations, we identified 51 (40%) cases with alterations in RAS pathway genes (RAS+, mostly NF1, NRAS, KRAS, and PTPN11 genes). In 79 homogeneously treated AML patients from this cohort, RAS+ status were associated with higher white blood cell count, higher LDH, and reduced survival. In AML models of oncogenic addiction to RAS-MEK signaling, the MEK inhibitor trametinib demonstrated antileukemic activity in vitro and in vivo. However, the efficacy of trametinib was heterogeneous in ex vivo cultures of primary RAS+ AML patient specimens. From repurposing drug screens in RAS-activated AML cells, we identified pyrvinium pamoate, an anti-helminthic agent efficiently inhibiting the growth of RAS+ primary AML cells ex vivo, preferentially in trametinib-resistant PTPN11- or KRAS-mutated samples. Metabolic and genetic complementarity between trametinib and pyrvinium pamoate translated into anti-AML synergy in vitro. Moreover, this combination inhibited the propagation of RA+ AML cells in vivo in mice, indicating a potential for future clinical development of this strategy in AML