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Haploidentical (haplo-) donors and cord-blood (CB) stem cells provide alternative transplant options in patients lacking an HLA-matched donor. In case of relapse or graft failure after a first alternative allogeneic hematopoietic stem cell transplant (HSCT), a second alternative HSCT (HSCT2) is rarely considered due to a high risk of toxicity.A retrospective French multicentre study was performed, including patients with hematologic malignancies who underwent two consecutive HSCT from alternative donors. All data were exported from the national ProMISE database between 2000 and 2016.Forty-three patients (61.4%) received a CB-HSCT2 and 27 (38.6%) a haplo-HSCT2. Indications for HSCT were graft failure (51.4%) or disease progression (48.6%). Two-years probabilities of overall survival, progression-free survival and toxicity-related mortality were 18.5%, 17.8% and 55.8%, respectively. In multivariate analysis, complete remission status at HSCT2 and year of HSCT2 ≥ 2012 were significantly associated with a better outcome (with respectively hazard ratio [HR] = 0.42, p = .002 and HR = 0.5, p = .051).Neither the indication of HSCT2 nor the source of stem cell was more advantageous towards overall patient survival. A salvage haploidentical or cord-blood stem cell transplantation is a high-risk procedure, that may be considered for patients achieving a complete remission before receiving the second HSCT.

Chromosomal inversions have been shown to play a major role in a local adaptation by suppressing recombination between alternative arrangements and maintaining beneficial allele combinations. However, so far, their importance relative to the remaining genome remains largely unknown. Understanding the genetic architecture of adaptation requires better estimates of how loci of different effect sizes contribute to phenotypic variation. Here, we used three Swedish islands where the marine snail Littorina saxatilis has repeatedly evolved into two distinct ecotypes along a habitat transition. We estimated the contribution of inversion polymorphisms to phenotypic divergence while controlling for polygenic effects in the remaining genome using a quantitative genetics framework. We confirmed the importance of inversions but showed that contributions of loci outside inversions are of similar magnitude, with variable proportions dependent on the trait and the population. Some inversions showed consistent effects across all sites, whereas others exhibited site-specific effects, indicating that the genomic basis for replicated phenotypic divergence is only partly shared. The contributions of sexual dimorphism as well as environmental factors to phenotypic variation were significant but minor compared to inversions and polygenic background. Overall, this integrated approach provides insight into the multiple mechanisms contributing to parallel phenotypic divergence.

La conduite des veaux laitiers sous nourrices, développée en France depuis 2010, est de plus en plus répandue en agriculture biologique. Dans ce système, les génisses pâturent très précocement et avec leurs nourrices ce qui peut modifier l’épidémiologie des strongles gastro-intestinaux (SGI). L’objectif de cette étude était d’évaluer la dynamique d’infestation par les SGI des génisses pâturant avec leurs nourrices durant la première saison de pâturage (SP1) et ses conséquences durant la seconde saison (SP2). Dans le nord-ouest de la France, 74 lots de 3 à 40 génisses de SP1 ont été suivis en 2018 ou 2019 et 34 lots de génisses en SP2 ont été suivis en 2020. Trois indicateurs parasitaires (coprologie, pepsinogène sérique, anticorps anti-Ostertagia) ont été mesurés en fin de SP1 en 2018, à 4 reprises en 2019 et à 3 reprises en 2020. Les génisses ont été mises à l’herbe à l’âge d’un mois en moyenne. La durée de la SP1 variait en fonction de la date de naissance. La durée de la SP2 était longue (278 ± 26 jours). Les valeurs moyennes de pepsinogène sérique et du ratio de densité optique (RDO) des taux d'anticorps anti-Ostertagia étaient globalement faibles en SP1 (respectivement 0,97 à 1,60 Unité Tyrosine et RDO de 0,23 à 0,71), indiquant une faible exposition des génisses aux SGI en présence des nourrices. Ceci est vraisemblablement dû à l’alimentation majoritairement lactée des jeunes, la présence de vaches nourrices immunes sur les parcelles et une conduite protectrice au pâturage. Les conséquences en SP2 des infestations sont très dépendantes de la durée de la SP1. Les génisses nées au printemps avec une longue SP1 (>180 jours), avaient de faibles niveaux d’excrétion fécale dès le milieu de la SP2 suggérant la mise en place d’une immunité vis-à-vis des SGI. Alors que les génisses nées à l’automne, avec une courte SP1 (< 90 jours) avaient une exposition aux SGI négligeable en SP1. En SP2, leurs indicateurs parasitaires correspondaient à ceux des génisses en SP1. Les niveaux de pepsinogène et de RDO étaient en revanche élevés en fin de SP2 quelle que soit la durée de la SP1 pour des raisons qui mériteraient d’être explorées plus en détail. En conclusion, avec une bonne gestion de pâturage, les génisses nées au printemps avaient peu de risque parasitaire. Une naissance plus tardive entraine une durée de SP1 plus courte, insuffisante pour le développement de l’immunité et pouvant entraîner un risque parasitaire en SP2.

Range expansion is a common natural phenomenon, which may be intensified by human-induced drivers such as climate change and alterations of habitat. The genetic consequences of range expansion are potentially major, and it is important to study known cases of range expansion to understand how human activities affect contemporary evolution, and to learn more about the genetic adaptive potential of species. The reed warbler (Acrocephalus scirpaceus) is a long-distance migratory bird breeding in Eurasia and wintering south of Sahara. It is currently expanding its range northwards, likely as a consequence of climate change. Interestingly, however, reed warblers have also recently colonised new territory southwards, following habitat restoration at the southern range margin. In this study, we investigate the genetic consequences of these two-directional range expansions with RAD-seq, looking at 10 populations from north to south in Europe. We investigate population structure and genome diversity, and assess the role of selection in divergence between populations across the species range. We do not find evidence of strong genetic structure in the reed warbler populations, and the youngest edge populations do not exhibit any substantial loss in genetic diversity, suggesting ongoing gene flow. On a smaller scale, the edge populations are the most genetically distinct, and we identify environmental disparity, especially in precipitation variability, as the main barrier of gene flow, to a greater extent than geographic distance. We find no evidence that the loci involved in population divergence and adaptation in the core populations are the same that are involved in adaptation at the range edges. Using three genome scan methods to identify selection, we found 49 SNPs putatively under selection, of which 33 were located in introns of 28 unique genes. Most of these are correlated with differences in climatic variables of temperature and precipitation. Some genome scan outliers show signs of being part of nascent selective sweeps, especially one which is distinct for the northern range edge. Our results suggest that in the reed warbler, contemporary range expansion has had little effect on molecular diversity and has been rapidly followed by local adaptation to climatic conditions, which could further corroborate the rapid pace at which colonisation of novel environments has occurred both northwards and southwards.

Helminth infections of cattle place significant burdens on livestock production and farm economic efficiency. Heavy infections are relatively easy to detect and treat with anthelmintics. However, subclinical infections have major but often hidden impacts on animals, necessitating more refined diagnostics to detect them and ideally inform farmers about the likely impact of anthelmintic treatment on animal and herd performance. Here, we review recent advances in diagnosing three major cattle helminth infections - gastrointestinal nematodes (GINs), liver flukes, and lungworms - and the search for subclinical infection thresholds to guide treatment decisions. Combining refined diagnostic thresholds with farm-specific information on grazing systems and animal history enables farmers to tailor helminth treatments to specific epidemiological circumstances, thereby limiting anthelmintic resistance (AR) and boosting agricultural efficiency and food security.