An optimized acetylcholine sensor for monitoring in vivo cholinergic activity, bioRxiv, 2019-12-03
The ability to directly measure acetylcholine (ACh) release is an essential first step towards understanding its physiological function. Here we optimized the GRABACh (GPCR-Activation–Based-ACh) sensor with significantly improved sensitivity and minimal downstream coupling. Using this sensor, we measured in-vivo cholinergic activity in both Drosophila and mice, revealing compartmental ACh signals in fly olfactory center and single-trial ACh dynamics in multiple regions of the mice brain under a variety of different behaviors
biorxiv neuroscience 100-200-users 2019Another look at microbe–metabolite interactions how scale invariant correlations can outperform a neural network, bioRxiv, 2019-12-02
AbstractMany scientists are now interested in studying the correlative relationships between microbes and metabolites. However, these kinds of analyses are complicated by the compositional (i.e., relative) nature of the data. Recently, Morton et al. proposed a neural network architecture called mmvec to predict metabolite abundances from microbe presence. They introduce this method as a scale invariant solution to the integration of multi-omics compositional data, and claim that “mmvec is the only method robust to scale deviations”. We do not doubt the utility of mmvec, but write in defense of simple linear statistics. In fact, when used correctly, correlation and proportionality can actually outperform the mmvec neural network.
biorxiv bioinformatics 0-100-users 2019Spontaneous generation of face recognition in untrained deep neural networks, bioRxiv, 2019-12-02
AbstractFace-selective neurons are observed in the primate visual pathway and are considered the basis of facial recognition in the brain. However, it is debated whether this neuronal selectivity can arise spontaneously, or requires training from visual experience. Here, we show that face-selective neurons arise spontaneously in random feedforward networks in the absence of learning. Using biologically inspired deep neural networks, we found that face-selective neurons arise under three different network conditions one trained using non-face natural images, one randomized after being trained, and one never trained. We confirmed that spontaneously emerged face-selective neurons show the biological view-point-invariant characteristics observed in monkeys. Such neurons suddenly vanished when feedforward weight variation declined to a certain level. Our results suggest that innate face-selectivity originates from statistical variation of the feedforward projections in hierarchical neural networks.
biorxiv neuroscience 0-100-users 2019The hematopoietic landscape at single-cell resolution reveals unexpected stem cell features in naked mole-rats, bioRxiv, 2019-12-02
SUMMARYNaked mole-rats are the longest-lived rodents endowed with resistance to cancer and age-related diseases, yet their stem cell characteristics remain enigmatic. We profiled the naked mole-rat hematopoietic system down to single-cell resolution, and identified several unique features likely contributing to longevity. In adult naked mole-rats red blood cells are formed in spleen and marrow, a neotenic feature beneficial for hypoxic environments and to prevent anemia. Platelet numbers are lower compared to short-lived mice, which may preclude age-related platelet increase and thrombosis. T cells mature in thymus and lymph nodes, providing a supply of T cells after age-related thymus involution. The pool of quiescent stem cells is higher than in mice, and HSCs overexpress an oxidative phosphorylation signature, revealing a new paradigm of stem cell metabolism to benefit longevity and oppose oncogenesis. Our work provides a platform to study immunology and stem cell biology in an animal model of healthy aging.HIGHLIGHTS<jatslist list-type=bullet><jatslist-item>Flow cytometry labelling panel to purify viable naked mole-rat HSPCs<jatslist-item><jatslist-item>The spleen as the major site of erythropoiesis in the naked mole-rat<jatslist-item><jatslist-item>Naked mole-rats show extrathymic T-cell development under homeostatic conditions<jatslist-item><jatslist-item>Naked mole-rat hematopoietic stem cells (HSCs) have high OXPHOS activity<jatslist-item>
biorxiv immunology 0-100-users 2019Frequent extrachromosomal oncogene amplification drives aggressive tumors, bioRxiv, 2019-11-29
Extrachromosomal DNA (ecDNA) amplification promotes high oncogene copy number, intratumoral genetic heterogeneity, and accelerated tumor evolution1–3, but its frequency and clinical impact are not well understood. Here we show, using computational analysis of whole-genome sequencing data from 1,979 cancer patients, that ecDNA amplification occurs in at least 26% of human cancers, of a wide variety of histological types, but not in whole blood or normal tissue. We demonstrate a highly significant enrichment for oncogenes on amplified ecDNA and that the most common recurrent oncogene amplifications arise on ecDNA. EcDNA amplifications resulted in higher levels of oncogene transcription compared to copy number matched linear DNA, coupled with enhanced chromatin accessibility. Patients whose tumors have ecDNA-based oncogene amplification showed increase of cell proliferation signature activity, greater likelihood of lymph node spread at initial diagnosis, and significantly shorter survival, even when controlled for tissue type, than do patients whose cancers are not driven by ecDNA-based oncogene amplification. The results presented here demonstrate that ecDNA-based oncogene amplification plays a central role in driving the poor outcome for patients with some of the most aggressive forms of cancers.
biorxiv cancer-biology 0-100-users 2019The frequency gradient of human resting-state brain oscillations follows cortical hierarchies, bioRxiv, 2019-11-28
AbstractThe human cortex is characterized by local morphological features such as cortical thickness, myelin content and gene expression that change along the posterior-anterior axis. We investigated if these structural gradients are associated with a similar gradient in a prominent feature of brain activity – namely the frequency of brain oscillations. In resting-state MEG recordings from healthy participants (N=187), we found that the strongest peak frequency in a brain area decreases significantly, gradually and robustly along the posterior-anterior axis following the global hierarchy from early sensory to higher-order areas. This spatial gradient of peak frequency was significantly anticorrelated with the cortical thickness of corresponding areas representing a proxy of the cortical hierarchical level. This result indicates that the intrinsic ‘resonance’ frequency decreases systematically from early sensory to higher-order areas and establishes a new structure-function relationship pertaining to brain oscillations as a core organizational principle that may underlie hierarchical specialization in the brain.
biorxiv neuroscience 100-200-users 2019