Biology subjects

White, K. A.

Publications and source records attributed to White, K. A..

2 recordsLinked to original sources

bioRxiv2017

A cortical pathway modulates sensory input into the olfactory striatum

Sensory cortices process stimuli in manners essential for perception. The piriform primary olfactory cortex (PCX) extends dense association fibers into the ventral striatums olfactory tubercle (OT), yet the function of this cortico-striatal pathway is unknown. We optically stimulated channelrhodopsin-transduced PCX glutamatergic neurons or their association fibers while recording OT neural activity in mice performing an olfactory task. Activation of PCX neurons or their association fibers within the OT controlled the firing of some OT neurons and bidirectionally modulated odor coding dependent upon the neurons intrinsic odor responsivity. Further, patch clamp recordings and retroviral tracing from D1 and D2 dopamine receptor-expressing OT medium spiny neurons revealed this input can be monosynaptic and that both cell types receive most of their input from a specific spatial zone localized within the ventro-caudal PCX. These results demonstrate that the PCX functionally accesses the direct and indirect pathways of the basal ganglia within the OT.

neuroscience↗

bioRxiv2017

Prominent Features Of The Amino Acid Mutation Landscape In Cancer

Cancer can be viewed as a set of different diseases with distinctions based on tissue origin, driver mutations, and genetic signatures. Accordingly, each of these distinctions have been used to classify cancer subtypes and to reveal common features. Here, we present a different analysis of cancer based on amino acid mutation signatures. Non-negative Matrix Factorization and principal component analysis of 29 cancers revealed six amino acid mutation signatures, including four signatures that were dominated by either arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. Sample-level analyses reveal that while some cancers are heterogeneous, others are largely dominated by one type of mutation. Using a non-overlapping set of samples from the COSMIC somatic mutation database, we validate five of six mutation signatures, including signatures with prominent arginine to histidine (Arg>His) or glutamate to lysine (Glu>Lys) mutations. This suggests that our classification of cancers based on amino acid mutation patterns may provide avenues of inquiry pertaining to specific protein mutations that may generate novel insights into cancer biology.

bioinformatics↗