bioRxiv Science⌕ Search

Biology subjects

Noh, S. M.

Publications and source records attributed to Noh, S. M..

5 recordsLinked to original sources

Genome sequencing and multi-stage, blood-feeding, and tissue-specific transcriptome atlas of the Rocky Mountain wood tick provide a critical resource for this vector

Dermacentor andersoni, the Rocky Mountain wood tick, is an important vector for pathogens impacting human and animal health, including bovine anaplasmosis, Colorado tick fever, and Rocky Mountain spotted fever. A better understanding of the biology of this tick is needed for developing disease prevention and vector control strategies. A reference genome was assembled for D. andersoni using high-fidelity (HiFi) long-read PacBio sequences and Hi-C contact mapping, yielding a contiguous assembly in which most contigs matched one of 11 chromosomes. Genome annotation by the NCBI eukaryotic genome annotation pipeline revealed high gene content completeness, yielding a genome completeness score of 94.0% using the Arachnida ortholog dataset. Following genome sequencing, we identified specific genes involved in blood feeding across a range of tissue types and life stages for D. andersoni. To accomplish this, RNA-seq analysis was used to investigate differential gene expression across most organs in adult, nymphal, and larval D. andersoni before and after feeding. Based on this analysis, we identified several gene groups that are involved in blood feeding. Furthermore, we establish sex- and developmental-stage-specific transcriptional profiles. Collectively, this study advances knowledge of D. andersoni biology and enables the development of strategies to limit the spread of diseases transmitted by this tick.

genomics↗

A compressed code for memory discrimination

The ability to discriminate similar visual stimuli has been used as an important index of memory function. This ability is widely thought to be supported by expanding the dimensionality of relevant neural codes, such that neural representations for the similar stimuli are maximally distinct, or "separated." An alternative hypothesis is that discrimination is supported by lossy compression of visual inputs, efficiently coding sensory information by discarding seemingly irrelevant details. A benefit of compression, relative to expansion, is that it allows the individual to efficiently retain fewer essential dimensions underlying stimulus variation--a process linked to higher-order visual processing--without hindering discrimination. Under the compression hypothesis, pattern separation is facilitated when more information from similar stimuli can be discarded, rather than preserving more information about distinct stimulus dimensions. We test the compression versus expansion hypotheses by predicting performance on the canonical mnemonic similarity task. First, we train neural networks to compress perceptual and semantic factors of stimuli, and measure lossiness of those representations using the mathematical framework underlying compression. Consistent with the compression hypothesis, and not the expansion hypothesis, we find that greater lossiness predicts the ease and performance of lure discrimination, particularly in later layers of convolutional neural networks shown to predict brain activity in the higher-order visual stream. We then empirically confirm these predictions across two sets of images, four behavioral datasets, and alternative metrics of lossiness. Finally, using task fMRI data, we identify signatures of lossy compression--neural dimensionality reduction and information loss--in the higher-order visual stream regions V4 and IT as well as hippocampal subregions dentate gyrus/CA3 and CA1 associated with lure discrimination performance. These results suggest lossy compression may support mnemonic discrimination behavior by discarding redundant and overlapping information.

neuroscience↗

Multiplex genome editing eliminates the Warburg Effect without impacting growth rate in mammalian cells

The Warburg effect is ubiquitous in proliferative mammalian cells, including cancer cells, but poses challenges for biopharmaceutical production, as lactate accumulation inhibits cell growth and protein production. Previous efforts to eliminate lactate production via knockout have failed in mammalian bioprocessing since lactate dehydrogenase has proven essential. However, here we eliminated the Warburg effect in Chinese hamster ovary (CHO) and HEK293 cells by simultaneously knocking out lactate dehydrogenase and regulators involved in a negative feedback loop that typically inhibits pyruvate conversion to acetyl-CoA. In contrast to long-standing assumptions about the role of aerobic glycolysis, Warburg-null cells maintain wildtype growth rate while producing negligible lactate. Further characterization of Warburg-null CHO cells showed a compensatory increase in oxygen consumption, a near total reliance on oxidative metabolism, and higher cell densities in fed-batch cell culture. These cells remained amenable for production of diverse biotherapeutic proteins, reaching industrially relevant titers and maintaining product glycosylation. Thus, the ability to eliminate the Warburg effect is an important development for biotherapeutic production and provides a tool for investigating a near-universal metabolic phenomenon.

bioengineering↗

The unfolded protein response triggers the ancestral immune deficiency pathway

The insect immune deficiency (IMD) pathway is a defense mechanism that senses and responds to Gram negative bacteria. Ticks lack genes encoding upstream components that initiate the IMD pathway. Despite this deficiency, core signaling molecules are present and functionally restrict tick-borne pathogens. The molecular events preceding activation remain undefined. Here, we show that the Unfolded Protein Response (UPR) initiates the IMD network in Ixodes scapularis ticks. The endoplasmic reticulum (ER) stress receptor, IRE1, is phosphorylated in response to tick-borne bacteria, but does not splice the mRNA encoding XBP1. Instead, through protein modeling and reciprocal pulldowns, we show that Ixodes IRE1 complexes with TRAF2. Disrupting IRE1-TRAF2 signaling blocks IMD pathway activation and diminishes the production of reactive oxygen species. Through in vitro, in vivo, and ex vivo techniques we demonstrate that the UPR-IMD pathway circuitry limits the Lyme disease-causing spirochete Borrelia burgdorferi and the rickettsial agents Anaplasma phagocytophilum and A. marginale (anaplasmosis). Altogether, our study uncovers a novel linkage between the UPR and the IMD pathway in ticks.

immunology↗

Sequence and immunologic conservation of Anaplasma marginale OmpA within strains from Ghana as compared to the predominant OmpA variant

A primary challenge in developing effective vaccines against obligate, intracellular, bacterial tick-borne pathogens that establish persistent infection is the identification of antigens that cross protect against multiple strains. In the case of Anaplasma marginale, the most prevalent tick-borne pathogen of cattle found worldwide, OmpA is an adhesin and thus a promising vaccine candidate. We sequenced ompA from cattle throughout Ghana naturally infected with A. marginale in order to determine the degree of variation in this gene in an area of suspected high genetic diversity. We compared the Ghanaian sequences with those available from N. America, Mexico, Australia and Puerto Rico. When considering only amino acid changes, three unique Ghanaian OmpA variants were identified. In comparison, strains from all other geographic regions, except one, shared a single OmpA variant, Variant 1, which differed from the Ghanaian variants. Next, using recombinant OmpA based on Variant 1, we determined that amino acid differences in OmpA in Ghanaian cattle as compared to OmpA Variant 1 did not alter the binding capacity of antibody directed against OmpA Variant 1, supporting the value of OmpA as a highly conserved vaccine candidate.

microbiology↗