Effects of parasite and historic driven selection on the diversity and structure of a MHC-II gene in a small mammal species (Peromyscus leucopus) undergoing range expansion.

Abstract Genetic diversity may decrease from the centre to the margin of a species distribution range due to neutral stochastic processes. Selection may also alter genetic diversity in non-neutral markers, such as genes associated with the immune system. Both neutral processes and selection on the immune system are thus expected to affect the spatial distribution of such markers, but the relative strength of each has been scarcely studied. Here, we compared the diversity of a neutral marker (mitochondrial cytochrome b)and a selected marker (DRB gene from the MHC-II), in eastern-North American populations of white-footed mice (Peromyscus leucopus), a species known for its role of main reservoir of the Lyme disease. We observed distinct phylogeographic patterns with these two markers, which may be the result of selection pressure acting upon the DRB gene. As predicted by the central marginal hypothesis, we observed a loss of neutral genetic diversity toward the margin of the species distribution. A decrease in diversity was also observed for the DRB gene, likely due to genetic drift and positive selection operated by helminth parasites. Such a loss in genetic diversity at the range margin may slow down the ongoing expansion of P. leucopus, by counterbalancing the effect of global warming on the mouse survival at higher latitude

Mid-Neogene Mediterranean marine-continental correlations: an alternative interpretation

Recent revised magnetostratigraphic and astrochronologic calibrations of several calcareous planktonic microfossil datum events (in particular Coccolithus miopelagicus and Neogloboquadrina acostaensis) combined with our magnetobiostratigraphic investigation of a 10 m-thick section at Ecotet, near Lyon (France), in which terrestrial micromammals (Vallesian Zone MN9) are intercalated with calcareous nannoplankton and planktonic foraminifera belonging to Zones NN6-NN8 and N14-15 (=M11 and M12), respectively, lead us to question the recent recalibration by Krijgsman et al. [(1996) Eart Planet. Sci. Lett. 142, 367-380) of the Aragonian/Vallesian (MN7-8/MN9) boundary with Chron C5r.1r (~11.1 Ma) and the lower/upper Vallesian (MN9/10) boundary with Chron C4Ar.2n (~9.6-9.7 Ma). Ecotet, with a uniform reverse polarity, is shown to be assignable uniquely to Chron C5r. Interregional correlation of Ecotet with Mediterranean terrestrial stratigraphies indicates that Progonomys (whose First Occurrence (FO) has been traditionally placed in Mediterranean Mammal Zone MN10) was already present in Mediterranean Zone MN9 at ~11.4 Ma and did not experience a 2 million-year delay in its putative prochoresis from Asia

On Quantum Effects in Soft Leptogenesis

It has been recently shown that quantum Boltzman equations may be relevant for leptogenesis. Quantum effects, which lead to a time-dependent CP asymmetry, have been shown to be particularly important for resonant leptogenesis when the asymmetry is generated by the decay of two nearly degenerate states. In this work we investigate the impact of the use of quantum Boltzman equations in the framework ``soft leptogenesis'' in which supersymmetry soft-breaking terms give a small mass splitting between the CP-even and CP-odd right-handed sneutrino states of a single generation and provide the CP-violating phase to generate the lepton asymmetry.Comment: 15 pages, 4 figures. Replacement to match published versio

Body Shape and Life Style of the Extinct Balearic Dormouse Hypnomys (Rodentia, Gliridae): New Evidence from the Study of Associated Skeletons

Hypnomys is a genus of Gliridae (Rodentia) that occurred in the Balearic Islands until Late Holocene. Recent finding of a complete skeleton of the chronospecies H. morpheus (Late Pleistocene-Early Holocene) and two articulated skeletons of H. cf. onicensis (Late Pliocene) allowed the inference of body size and the calculation of several postcranial indexes. We also performed a Factorial Discriminant Analysis (FDA) in order to evaluate locomotory behaviour and body shape of the taxa. Using allometric models based on skull and tooth measurements, we calculated a body weight between 173 and 284 g for H. morpheus, and direct measurements of articulated skeletons yielded a Head and Body Length (HBL) of 179 mm and a Total Body Length of 295 mm for this species. In addition to the generally higher robustness of postcranial bones already recorded by previous authors, H. morpheus, similar to Canariomys tamarani, another extinct island species, displayed elongated zygopodium bones of the limbs and a wider distal humerus and femur than in an extant related taxon, Eliomys quercinus. Indexes indicated that Hypnomys was more terrestrial and had greater fossorial abilities than E. quercinus. This was also corroborated by a Discriminant Analysis, although no clear additional inference of locomotory abilities could be calculated

Mosaic Convergence of Rodent Dentitions

BACKGROUND:Understanding mechanisms responsible for changes in tooth morphology in the course of evolution is an area of investigation common to both paleontology and developmental biology. Detailed analyses of molar tooth crown shape have shown frequent homoplasia in mammalian evolution, which requires accurate investigation of the evolutionary pathways provided by the fossil record. The necessity of preservation of an effective occlusion has been hypothesized to functionally constrain crown morphological changes and to also facilitate convergent evolution. The Muroidea superfamily constitutes a relevant model for the study of molar crown diversification because it encompasses one third of the extant mammalian biodiversity. METHODOLOGY/PRINCIPAL FINDINGS:Combined microwear and 3D-topographic analyses performed on fossil and extant muroid molars allow for a first quantification of the relationships between changes in crown morphology and functionality of occlusion. Based on an abundant fossil record and on a well resolved phylogeny, our results show that the most derived functional condition associates longitudinal chewing and non interlocking of cusps. This condition has been reached at least 7 times within muroids via two main types of evolutionary pathways each respecting functional continuity. In the first type, the flattening of tooth crown which induces the removal of cusp interlocking occurs before the rotation of the chewing movement. In the second type however, flattening is subsequent to rotation of the chewing movement which can be associated with certain changes in cusp morphology. CONCLUSION/SIGNIFICANCE:The reverse orders of the changes involved in these different pathways reveal a mosaic evolution of mammalian dentition in which direction of chewing and crown shape seem to be partly decoupled. Either can change in respect to strong functional constraints affecting occlusion which thereby limit the number of the possible pathways. Because convergent pathways imply distinct ontogenetic trajectories, new Evo/Devo comparative studies on cusp morphogenesis are necessary

Phenomenology of Light Sneutrino Dark Matter in cMSSM/mSUGRA with Inverse Seesaw

We study the possibility of a light Dark Matter (DM) within a constrained Minimal Supersymmetric Standard Model (cMSSM) framework augmented by a SM singlet-pair sector to account for the non-zero neutrino masses by inverse seesaw mechanism. Working within a 'hybrid' scenario with the MSSM sector fixed at high scale and the singlet neutrino sector at low scale, we find that, contrary to the case of the usual cMSSM where the neutralino DM cannot be very light, we can have a light sneutrino DM with mass below 100 GeV satisfying all the current experimental constraints from cosmology, collider as well as low-energy experiments. We also note that the supersymmetric inverse seesaw mechanism with sneutrino as the lightest supersymmetric partner can have enhanced same-sign dilepton final states with large missing transverse energy (mET) coming from the gluino- and squark-pair as well as the squark-gluino associated productions and their cascade decay through charginos. We present a collider study for the same-sign dilepton+jets+mET signal in this scenario and propose some distinctions with the usual cMSSM. We also comment on the implications of such a light DM scenario on the invisible decay width of an 125 GeV Higgs boson.Comment: 24 pages, 4 figures, 7 tables; matches published versio

miR-15a-5p and miR-21-5p contribute to chemoresistance in cytogenetically normal acute myeloid leukaemia by targeting PDCD4, ARL2 and BTG2

Cytarabine and daunorubicin are old drugs commonly used in the treatment of acute myeloid leukaemia (AML). Refractory or relapsed disease because of chemotherapy resistance is a major issue. microRNAs (miRNAs) were incriminated in resistance. This study aimed to identify miRNAs involved in chemoresistance in AML patients and to define their target genes. We focused on cytogenetically normal AML patients with wild-type NPM1 without FLT3-ITD as the treatment of this subset of patients with intermediate-risk cytogenetics is not well established. We analysed baseline AML samples by small RNA sequencing and compared the profile of chemoresistant to chemosensitive AML patients. Among the miRNAs significantly overexpressed in chemoresistant patients, we revealed miR-15a-5p and miR-21-5p as miRNAs with a major role in chemoresistance in AML. We showed that miR-15a-5p and miR-21-5p overexpression decreased apoptosis induced by cytarabine and/or daunorubicin. PDCD4, ARL2 and BTG2 genes were found to be targeted by miR-15a-5p, as well as PDCD4 and BTG2 by miR-21-5p. Inhibition experiments of the three target genes reproduced the functional effect of both miRNAs on chemosensitivity. Our study demonstrates that miR-15a-5p and miR-21-5p are overexpressed in a subgroup of chemoresistant AML patients. Both miRNAs induce chemoresistance by targeting three pro-apoptotic genes PDCD4, ARL2 and BTG2

Reduced anticoagulation targets in extracorporeal life support (RATE):study protocol for a randomized controlled trial

BackgroundAlthough life-saving in selected patients, ECMO treatment still has high mortality which for a large part is due to treatment-related complications. A feared complication is ischemic stroke for which heparin is routinely administered for which the dosage is usually guided by activated partial thromboplastin time (aPTT).However, there is no relation between aPTT and the rare occurrence of ischemic stroke (1.2%), but there is a relation with the much more frequent occurrence of bleeding complications (55%) and blood transfusion. Both are strongly related to outcome.MethodsWe will conduct a three-arm non-inferiority randomized controlled trial, in adult patients treated with ECMO. Participants will be randomized between heparin administration with a target of 2–2.5 times baseline aPTT, 1.5–2 times baseline aPTT, or low molecular weight heparin guided by weight and renal function. Apart from anticoagulation targets, treatment will be according to standard care. The primary outcome parameter is a combined endpoint consisting of major bleeding including hemorrhagic stroke, severe thromboembolic complications including ischemic stroke, and mortality at 6 months.DiscussionWe hypothesize that with lower anticoagulation targets or anticoagulation with LMWH during ECMO therapy, patients will have fewer hemorrhagic complications without an increase in thromboembolic complication or a negative effect on their outcome. If our hypothesis is confirmed, this study could lead to a change in anticoagulation protocols and a better outcome for patients treated with ECMO.Trial registrationClinicalTrials.gov NCT04536272. Registered on 2 September 2020. Netherlands Trial Register NL796