Search bioRxiv⌕ Search

Biology subjects

Ballard, J.

Publications and source records attributed to Ballard, J..

3 recordsLinked to original sources

Coral demographic performances in New Caledonia, a video transect approach to operationalize imagery-based investigation of population and community dynamics

Demographic studies that quantify species performances for survival, growth, and reproduction are powerful means to understand and predict how species and communities respond to environmental change through the characterization of population dynamics and sources of demographic bottlenecks. However, demographic studies require fine-scale surveys of populations in the field, and are often too effort-intensive to be replicable at large scale and in the long-term. To surpass this obstacle, we developed a digital approach for extracting demographic data on species abundances, sizes, and positions within video-transects, facilitating back-from-the-field data acquisitions on population and community dynamics from video surveys. The approach is based on manual coral identification, size-measurements, and mapping along video-transects, mimicking what is traditionally performed in the field, thought it can be automated in the future with the deployment of artificial intelligence. We illustrate our approach with the characterizations of species demographic performances using surveys of a reef-building coral community in New Caledonia recorded with underwater cameras, therefore optimizing time spent in the field. The results provide quantitative measures of coral community composition and demographic performances as key ecological indicators of coral reef health, shed light on species life strategies and constraints to their demographics, and open paths for further quantitative investigations. Key findings include the diversity of species life strategies in terms of relative investment in survival, growth, and reproduction found among taxa dominating the coral community, indicating the diversity of demographic paths to ecological success and that several species have adapted mechanisms to prevail under limiting hydrodynamic environments. Our approach facilitates image-based extractions of demographic data, helping to accelerate empirical endeavors in ecology and ecosystem management. Author summarySustainable ecosystem management requires comprehension of key ecological processes that affect species resilience. Accurate and reoccurring measurements of species helps us understand how they are responding to various environments and predict what might happen in the future. We developed a digital approach that mimics measurements traditionally performed in the field to measure species abundance, size, and distributions using video records of the ecosystems. This transition to imagery-based surveys helps researchers and managers acquire fine-scale ecological data while optimizing time spent in the field, particularly for studying remote and extreme environments where access is limited. We illustrate the application of our approach by characterizing the dynamics of a coral community in the vast tropical reef system of New Caledonia, where such evaluations of demographic processes controlling coral resilience are inexistent but necessary.

ecology↗

Development of an ASO therapy for Angelman syndrome by targeting an evolutionarily conserved region at the start of the UBE3A-AS transcript

Angelman syndrome is a devastating neurogenetic disorder for which there is currently no effective treatment. It is caused by mutations or epimutations affecting the expression or function of the maternally inherited allele of the ubiquitin-protein ligase E3A (UBE3A) gene. The paternal UBE3A allele is imprinted in neurons of the central nervous system (CNS) by the UBE3A antisense (UBE3A-AS) transcript, which represents the distal end of the SNHG14 transcription unit. Reactivating the expression of the paternal UBE3A allele in the CNS has long been pursued as a therapeutic option for Angelman syndrome. Here, we designed and optimized antisense oligonucleotides (ASO) targeting an evolutionarily conserved region demarcating the start of the human UBE3A-AS transcript and show that ASOs targeting this region can reverse imprinting of UBE3A in cultured Angelman syndrome neurons and throughout the CNS of a non-human primate model. Findings from this study advanced the first investigational molecular therapy for Angelman syndrome into clinical development (ClinicalTrials.gov, NCT04259281). SUMMARYHere, we describe the preclinical studies supporting the first investigational molecular therapy for Angelman syndrome to advance into clinical development (ClinicalTrials.gov, NCT04259281).

genetics↗

Re-Evaluating One-step Generation of Mice Carrying Conditional Alleles by CRISPR-Cas9-Mediated Genome Editing Technology

CRISPR-Cas9 gene editing technology has considerably facilitated the generation of mouse knockout alleles, relieving many of the cumbersome and time-consuming steps of traditional mouse embryonic stem cell technology. However, the generation of conditional knockout alleles remains an important challenge. An earlier study reported up to 16% efficiency in generating conditional knockout alleles in mice using 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides (ssODN) (2sgRNA-2ssODN). We re-evaluated this method from a large data set generated from a consortium consisting of 17 transgenic core facilities or laboratories or programs across the world. The dataset constituted 17,887 microinjected or electroporated zygotes and 1,718 live born mice, of which only 15 (0.87%) mice harbored 2 correct LoxP insertions in cis configuration indicating a very low efficiency of the method. To determine the factors required to successfully generate conditional alleles using the 2sgRNA-2ssODN approach, we performed a generalized linear regression model. We show that factors such as the concentration of the sgRNA, Cas9 protein or the distance between the placement of LoxP insertions were not predictive for the success of this technique. The major predictor affecting the methods success was the probability of simultaneously inserting intact proximal and distal LoxP sequences, without the loss of the DNA segment between the two sgRNA cleavage sites. Our analysis of a large data set indicates that the 2sgRNA-2ssODN method generates a large number of undesired alleles (>99%), and a very small number of desired alleles (<1%) requiring, on average 1,192 zygotes.

genetics↗