Biology subjects

Herman, N.

Publications and source records attributed to Herman, N..

4 recordsLinked to original sources

bioRxiv2026

Epithelial mesenchymal transition initiates precancer states in BRCA1 mutation carriers

Epithelial-to-mesenchymal transition (EMT) is activated to equip cells with the capacity to adapt to and escape hostile conditions. While EMT is required for cancer progression, its role in breast cancer initiation remains elusive. Given the basal-like phenotype of breast cancers arising in female carriers of germline BRCA1 pathogenic variants (BRCA1 carriers), we hypothesized that enhanced EMT susceptibility underlies precancerous initiation in mammary epithelium. Perturbation of patient-derived normal mammary organoids from BRCA1 carriers and non-carriers with inflammatory cytokines induced copy number variations (CNV) and the acquisition of oncogenic mutations in both groups. However, in organoids derived from BRCA1 carriers, cytokine exposure induced morphological, transcriptomic, and functional EMT, accompanied by a transition to basal-like phenotype. Concomitant DNA damage accumulation in organoids from BRCA1-carriers demonstrated PARP inhibitor sensitivity. EMT-primed states were identified in a subpopulation of normal mammary epithelium from BRCA1 carriers. We demonstrate the utility of patient-derived normal BRCA1 heterozygous mammary organoids to reveal a plastic, high-risk epithelial state that is associated with a transient, targetable vulnerability.

cancer biology↗

bioRxiv2023

Dog Ecology and Rabies Knowledge, Attitude and Practice (KAP) in the Northern Communal Areas of Namibia

In 2021, a comprehensive dog demographic questionnaire combined with a KAP survey were conducted in the northern communal areas (NCAs) of Namibia with the aim of gaining a better understanding of dog populations, owner behaviour, and knowledge, attitudes and practices (KAP) relating to rabies. The survey of 3,726 households across the eight regions of the NCAs provided insights that will inform interventions on order to improve human rabies prevention and Namibias dog rabies control strategy. The results showed a relatively low average human/dog ratio (HDR) of 5.4:1 indicating a surprisingly high dog population of at least 272,000 dogs in the NCAs, 93% of which appear to be owned but are free-roaming. Data analysis revealed opportunities but also highlighted needs for improvements in rabies surveillance and mass dog vaccinations. Although knowledge, attitude, and practice scores towards epidemiologic and clinical aspects, human rabies prevention, and canine rabies vaccination were deemed to be acceptable, the survey nevertheless revealed deficiencies in some of the population. Interestingly, data seemed to indicate a certain number of unreported human rabies cases. Other findings included the very high number of dogs. However, only 50% of dog-owning households reported having vaccinated their dogs. In order to address these issues, the planning, announcement, and implementation of mass dog vaccination campaigns need to be adapted to achieve adequate vaccination coverage. Another focus needs to be on rabies awareness and education if Namibia is to be significantly contributing to the global goal of "Zero by 30". Author SummaryAs a neglected disease, rabies remains a major One Health problem in Africa and Asia. Here we report the results of an extensive community survey on dog ownership and knowledge, attitudes and practices (KAP) related to rabies control and prevention, covering the Northern Communal Areas of Namibia. Our results showed that the dog population is large with a human/dog ratio (HDR) of 5.4:1, of which the vast majority is free-roaming thus supporting disease transmission but complicating control efforts. The majority of people across this part of Namibia were aware of rabies and had acceptable levels of attitudes and practices. While dog bite incidences per 100,000 people were high, ranging between 262 and 1,369, more than 90% of bite victims reported having visited a hospital after a bite incident. Still, gaps in dog rabies surveillance exist and incomplete or missing post exposure prophylaxes caused human casualties and call for ongoing interventions aimed at increasing knowledge and awareness.

microbiology↗

bioRxiv2021

The chromatin factor ROW cooperates with BEAF-32 in regulating long-range genes

Insulator proteins located at the boundaries of topological associated domains (TAD) are involved in regulating chromatin loops. Yet, how chromatin loops contribute to transcription regulation is still not clear. Here we show that Relative-of-WOC (ROW) is essential for the long-range transcription regulation mediated by the Boundary Element-Associated Factor of 32kD (BEAF-32). We found that ROW physically interacts with heterochromatin proteins (HP1b and HP1c) and the insulator protein BEAF-32. The co-localization happens at TAD boundaries where ROW, through its AT-hooks motifs, binds AT-rich sequences flanked by BEAF-32 binding sites and motifs. Knockdown of row resulted in downregulation of genes that are long-range targets of BEAF-32 and bound indirectly by ROW (without binding motif). Analysis of high- throughput chromosome conformation capture (Hi-C) data revealed long-range interactions between promoters of housekeeping genes bound directly by ROW and promoters of developmental genes bound indirectly by ROW. Thus, our results show cooperation between BEAF-32 and the ROW complex, which includes HP1 proteins, to regulate the transcription of developmental and inducible genes by chromatin loops.

genomics↗

bioRxiv2017

The industrial anaerobe Clostridium acetobutylicum uses polyketides to regulate butanol production and differentiation

Polyketides are an important class of bioactive small molecules valued not only for their diverse therapeutic applications, but also for their role in controlling interesting biological phenotypes in their producing organisms. While numerous examples of polyketides derived from aerobic organisms exist, only a single family of polyketides has been identified from anaerobic organisms. Here we uncover a novel family of polyketides native to the anaerobic bacterium Clostridium acetobutylicum, an organism well-known for its historical use as an industrial producer of the organic solvents acetone, butanol, and ethanol. Through mutational analysis and chemical complementation assays, we demonstrate that these polyketides influence butanol production and act as chemical triggers of sporulation and granulose accumulation in this strain. This study represents a significant addition to the body of work demonstrating the existence and importance of polyketides in anaerobes, and showcases a novel strategy of manipulating the secondary metabolism of an organism to improve traits significant for industrial applications.

microbiology↗