Biology subjects

Jacob, B.

Publications and source records attributed to Jacob, B..

5 recordsLinked to original sources

bioRxiv2023

Significant reduction in blackfly bites following implementation of Slash and Clear: An option to consider for onchocerciasis elimination in areas of persistent transmission

BackgroundAlthough "Slash and Clear" has proven effective in reducing blackfly densities in low transmission foci, the impact of this strategy in high transmission settings with large rivers and important vector densities remains to be demonstrated. Methods/Principal findingsA controlled before-and-after community-based intervention comprising two arms (Bayomen as control site and Biatsota as intervention site) was carried out in the Mbam Valley (Centre Region, Cameroon). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Before the intervention, a total of 36,273 and 29,041 blackflies were collected in Bayomen and Biatsota, respectively. After the intervention period, the total blackfly density in the intervention site decreased from 29,041 to 20,011 (31.1% reduction), while an increase of 2{middle dot}7% was observed in the control site (from 36,273 to 37,248). The Poisson mixed regression model shows that the reduction was significantly greater in the intervention site than in the control site (p<0.0005). Conclusions/SignificanceThis study showed that "Slash and Clear" approach is feasible and has a significant impact on vector densities in a high transmission setting. Further studies are needed to investigate the long-term impact of this vector control approach, and how this promising strategy can be scaled-up and sustained until elimination of onchocerciasis. Author summaryRiver blindness persists in some foci in Cameroon despite more than two decades of ivermectin-based preventive chemotherapy. Mass drug administration (MDA) appears insufficient to interrupt onchocerciasis transmission in these hotspots, and should be complemented by vector control, the most promising alternative strategy to date. In 2018, the effectiveness of a new community-based vector control approach, known as slash and clear, was demonstrated. This strategy involves the removal of trailing vegetation at breeding sites, a primary attachment points for blackfly larvae. In this study, we show that this environment-friendly intervention is feasible and has a significant impact on blackfly densities in high transmission settings. This promising intervention can be combined with regular annual ivermectin-based preventive chemotherapy to accelerate onchocerciasis elimination.

ecology↗

bioRxiv2022

Cryo-electron tomography and deep learning-based denoising reveal native chromatin landscapes of interphase nuclei

The chromatin machinery, with DNA-histone assembly and further folding of nucleosome chains, influences DNA availability for functional interactions necessary to the regulation of transcription, DNA replication and repair. Despite models based on in vitro studies, the nucleosome chain geometry within the crowded cell nucleus remains elusive. Using cryo-electron tomography of thin vitreous sections, we directly observed the path of nucleosomal and linker DNA in situ in intact flash-frozen organism - Drosophila embryo. We quantified linker length and curvature characterizing an irregular zig-zag chromatin folding motif, with a low degree of linker bending. Additionally, nucleosome conformational variability with non-canonical structures and non-octameric particles were observed as individual objects, without structure averaging, highlighting the high structural heterogeneity of native chromatin.

cell biology↗

bioRxiv2022

Investigating the Consistency of Extracellular Vesicle Production from Breast Cancer Subtypes Using CELLine Adherent Bioreactors

Extracellular vesicle (EV) research has grown rapidly in recent years, largely due to the potential use of EVs as liquid biopsy biomarkers or therapeutics. However, in-depth characterisation and validation of EVs produced using conventional in vitro cultures can be challenging due to the large area of cell monolayers and volumes of culture media required. To overcome this obstacle, multiple bioreactor designs have been tested for EV production with varying success, but the consistency of EVs produced over time in these systems has not been reported previously. In this study, we demonstrate that several breast cancer cell lines of different subtypes can be cultured simultaneously in space, resource, and time efficient manner using CELLine AD 1000 systems, allowing the consistent production of vast amounts of EVs for downstream experimentation. We report an improved workflow used for inoculating, maintaining, and monitoring the bioreactors, their EV production, and the characterisation of the EVs produced. Lastly, our proteomic analyses of the EVs produced throughout the lifetime of the bioreactors show that core EV-associated proteins are relatively consistent, with few minor variations over time, and that tracking the production of EVs may be a convenient method for indirectly monitoring the bioreactors health. These findings will aid future studies requiring the simultaneous production of large amounts of EVs from several cell lines of different subtypes of a disease and other EV biomanufacturing applications.

cancer biology↗

bioRxiv2020

C57BL6 mouse substrains demonstrate differences in susceptibility to the demyelinating effects of Cuprizone toxin

Advances in our understanding of cellular functions and phenotypes in the brain rely on technically robust experimental in vivo models with face validity towards human disease. The cuprizone toxin-induced demyelination model is widely used to investigate pathophysiological mechanisms of demyelinating and remyelinating phases of multiple sclerosis. The C57BL6 mouse is a common inbred strain used as the genetic background for genetically engineered and congenic mice. Substrains of C57BL6 mice sourced from distinct vendors are often treated as equivalent in research studies. Here, we demonstrated that an alternative dosing approach via oral gavage with a well-tolerated, lower dose of cuprizone resulted in significant differences in C57BL/6NTac (Taconic) over C57BL/6J (Jax) mice. With consistent dosing of cuprizone for 5 weeks, body weights were significantly affected in C57BL/6NTac versus C57BL/6J mice. DT-MRI showed significant demyelination in white matter regions in the C57BL/6NTac mice. Concomitantly, histology analysis illustrated increased microgliosis and proliferation in C57BL/6NTac compared with C57BL/6J mice. These observations suggest that the C57BL/6NTac substrain of C57BL6 mice is more vulnerable to cuprizone challenge. Genetic factors along with breeder source appear to influence susceptibility to cuprizone toxin. Thus, the awareness of the limitations of in vivo models in addition to informed decision making on the appropriate background substrain can greatly improve sensitivity and reproducibility of results and use for evaluating investigational therapeutics.

neuroscience↗

bioRxiv2018

Onecut factors and Pou2f2 regulate diversification and migration of V2 interneurons in the mouse developing spinal cord

Acquisition of proper neuronal identity and position is critical for the formation of neural circuits. In the embryonic spinal cord, cardinal populations of interneurons diversify into specialized subsets and migrate to defined locations within the spinal parenchyma. However, the factors that control interneuron diversification and migration remain poorly characterized. Here, we show that the Onecut transcription factors are necessary for proper diversification and distribution of the V2 interneurons in the developing spinal cord. Furthermore, we uncover that these proteins restrict and moderate the expression of spinal isoforms of Pou2f2, a transcription factor known to regulate B-cell differentiation. By gain- or loss-of-function experiments, we show that Pou2f2 contribute to regulate the position of V2 populations in the developing spinal cord. Thus, we uncovered a genetic pathway that regulates the diversification and the distribution of V2 interneurons during embryonic development.\n\nSignificance statementIn this study, we identify the Onecut and Pou2f2 transcription factors as regulators of spinal interneuron diversification and migration, two events that are critical for proper CNS development.

developmental biology↗