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Morales, H.

Publications and source records attributed to Morales, H..

4 recordsLinked to original sources

Inbreeding depression and population viability in a recovering population of Mauritius kestrels

Inbreeding depression (the reduction in fitness associated with inbreeding) has been demonstrated in a wide range of animals, but despite its ubiquity, is not an inevitable consequence of inbreeding. As a result, there is uncertainty about the extent to which inbreeding depression poses an ongoing risk to endangered species currently experiencing significant demographic recovery. Quantifying inbreeding depression will be critical if we want to understand these risks. A comprehensive quantification of the fitness costs of inbreeding requires detailed individual-based longitudinal data so lifetime impacts can be assessed. Here, we use an extraordinarily detailed long-term dataset on Mauritius kestrels (Falco punctatus) to explore inbreeding depression in a population currently experiencing significant demographic recovery. To do so, we constructed a social pedigree of 1,758 individuals and combined this with 1,240 nest records and 1,411 individual resighting histories to explore lifetime fitness effects over a 30-year period. Inbreeding increased significantly over time as the population recovered before stabilising. Inbred eggs were less likely to survive to fledging. Inbred adult male and female birds had significantly lower annual reproductive success than outbred individuals because of a lower annual egg-to-fledgling survival probability. This resulted in significantly lower lifetime reproductive success in inbred females but not males, which showed a negative trend. Population growth was negative and extinction risk increased slightly at current levels of inbreeding. These impacts will become more severe should inbreeding levels increase in the future, which is highly likely given ongoing genomic erosion. Taken together, our results demonstrate significant fitness costs associated with inbreeding in Mauritius kestrels, which pose an ongoing risk to population viability. This suggests that monitoring and managing inbreeding risks in endangered species will likely be required even in populations that are showing significant demographic recovery in response to conservation interventions.

ecology↗

Reprogramming human B cells with custom heavy chain antibodies

We describe a genome editing strategy to reprogram the immunoglobulin heavy chain (IgH) locus of human B cells to express custom molecules that respond to immunization. These heavy chain antibodies (HCAbs) comprise a custom antigen-recognition domain linked to an Fc domain derived from the IgH locus and can be differentially spliced to express either B cell receptor (BCR) or secreted antibody isoforms. The HCAb editing platform is highly flexible, supporting antigen-binding domains based on both antibody and non-antibody components, and also allowing alterations in the Fc domain. Using HIV Env protein as a model antigen, we show that B cells edited to express anti-Env HCAbs support the regulated expression of both BCRs and antibodies, and respond to Env antigen in a tonsil organoid model of immunization. In this way, human B cells can be reprogrammed to produce customized therapeutic molecules with the potential for in vivo amplification.

immunology↗

Homologous recombination-based genome editing by clade F AAVs is inefficient in the absence of a targeted DNA break

Adeno-associated virus (AAV) vectors are frequently used as donor templates for genome editing by homologous recombination. Although modification rates are typically under 1%, they are greatly enhanced by targeted double-stranded DNA breaks (DSBs). A recent report described clade F AAVs mediating high-efficiency homologous recombination-based editing in the absence of DSBs. The clade F vectors included AAV9 and a series isolated from human hematopoietic stem/progenitor cells (HSPCs). We evaluated these vectors by packaging homology donors into AAV9 and an AAVHSC capsid and examining their ability to insert GFP at the CCR5 or AAVS1 loci in human HSPCs and cell lines. As a control we used AAV6, which effectively edits HSPCs, but only when combined with a targeted DSB. Each AAV vector promoted GFP insertion in the presence of matched CCR5 or AAVS1 zinc finger nucleases (ZFNs), but none supported detectable editing in the absence of the nucleases. Rates of editing with ZFNs correlated with transduction efficiencies for each vector, implying no differences in the ability of donor sequences delivered by the different vectors to direct genome editing. Our results therefore do not support that clade F AAVs can perform high efficiency genome editing in the absence of a DSB.

synthetic biology↗

Low-Cost HPV Screening And The Prevalence Of Cervical Infection In Asymptomatic Populations In Guatemala

BackgroundA low cost and accurate method for detecting high-risk (HR) HPV is important to permit HPV testing for cervical cancer prevention. We validated a low-cost commercially available HPV method (H13, Hybribio, Hong Kong) and determined the distribution of HPV infections in over 1717 cancer-free women in Guatemala.\n\nMethodsH13 results were compared with two more established HPV tests: (Xpert (Cepheid) and SPF10-LIPA25 (DDL)) in 40 mainly known positive specimens. HR-HPV was detected in cervical samples from 1717 cancer-free women receiving Pap smears using the Hybribio realtime PCR assay of 13 HR types. Selected HPV positive samples were sequenced to determine viral type.\n\nResultsThe Hybribio H13 Assay showed 93% identical results with Xpert, and 89% with SPF10-LIPA25. A total of 13% (226/1717) of women tested HPV+. The highest prevalence was found in younger women (<30 years, 22 %) and older ones ([&ge;]60 years, 15%). The six most common HR-HPV types among the 148 HPV+ typed were HPV16 (22%), HPV18 (11%), HPV39 (11%), HPV58 (10%), HPV52 (8%), and HPV45 (8%).\n\nConclusionsThe Hybribio Assay was low cost, and accurate in testing for HR-HPV infection. As in most places, HPV16 was the most prevalent HR type in Guatemala and the age-specific prevalence curve peaked in younger ages.\n\nHighlightsO_LIA low cost and accurate method, Hybribio Assay, could be used for CC testing in low income regions.\nC_LIO_LIA total of 13% of cancer-free women were HPV+ and positivity was associated with younger age (<30 years old) in Guatemala.\nC_LIO_LIHPV16 was the major prevalent type.\nC_LI

molecular biology↗