Proteomics represents a significant challenge to separation scientists because of the diversity and complexity of proteins and peptides present in biological systems. Mass spectrometry as the central enabling technology in proteomics allows detection and identification of thousands of proteins and peptides in a single experiment. Liquid chromatography is recognized as an indispensable tool in proteomics research since it provides high-speed, high-resolution and high-sensitivity separation of macromolecules. In addition, the unique features of chromatography enable the detection of low-abundance species such as post-translationally modified proteins. Components such as phosphorylated proteins are often present in complex mixtures at vanishingly small concentrations. New chromatographic methods are needed to solve these analytical challenges, which are clearly formidable, but not insurmountable. This review covers recent advances in liquid chromatography, as it has impacted the area of proteomics. The future prospects for emerging chromatographic technologies such as monolithic capillary columns, high temperature chromatography and capillary electrochromatography are discussed.
The ability to recognize familiar visual objects is critical to survival. Neurons in inferotemporal (IT) cortex represent the percept of visual objects using a distributed axis code. However, the network code for the memory of visual objects remains elusive. Here, we measured neuronal responses to familiar and unfamiliar faces in two face patches, AM and PR. In both areas, familiar and unfamiliar faces were represented in distinct subspaces. The familiar face subspace was shifted relative to the unfamiliar face subspace at short latency and then distorted to increase neural distances between familiar faces at long latency. Our results suggest that memories of familiar faces are represented in IT and perirhinal cortex by a distinct long-latency code that is optimized to distinguish familiar identities.
Key points M1 intrinsically photosensitive retinal ganglion cells (ipRGCs) are known to encode absolute light intensity (irradiance) for non‐image‐forming visual functions (subconscious vision), such as circadian photoentrainment and the pupillary light reflex. It remains unclear how M1 cells respond to relative light intensity (contrast) and patterned visual signals. The present study identified a special form of contrast sensitivity (suppressed‐by‐contrast) in M1 cells, suggesting a role of patterned visual signals in regulating non‐image‐forming vision and a potential role of M1 ipRGCs in encoding image‐forming visual cues. The study also uncovered a synaptic mechanism and a retinal circuit mediated by vesicular glutamate transporter 3 (vGluT3) amacrine cells that underlie the suppressed‐by‐contrast response of M1 cells. M1 ipRGC subtypes (M1a and M1b) were revealed that are distinguishable based on synaptic connectivity with vGluT3 amacrine cells, receptive field properties, intrinsic photo sensitivity and membrane excitability, and morphological features, suggesting a division of visual tasks among discrete M1 subpopulations. Abstract The M1 type ipRGC (intrinsically photosensitive retinal ganglion cell) is known to encode ambient light signals for non‐image‐forming visual functions such as circadian photo‐entrainment and the pupillary light reflex. Here, we report that a subpopulation of M1 cells (M1a) in the mouse retina possess the suppressed‐by‐contrast (sbc) trigger feature that is a receptive field property previously found only in ganglion cells mediating image‐forming vision. Using optogenetics and the dual patch clamp technique, we found that vesicular glutamate transporter 3 (vGluT3) (vGluT3) amacrine cells make glycinergic, but not glutamatergic, synapses specifically onto M1a cells. The spatiotemporal and pharmacological properties of visually evoked responses of M1a cells closely matched the receptive field characteristics of vGluT3 cells, suggesting a major role of the vGluT3 amacrine cell input in shaping the sbc trigger feature of M1a cells. We found that the other subpopulation of M1 cells (M1b), which did not receive a direct vGluT3 cell input, lacked the sbc trigger feature, being distinctively different from M1a cells in intrinsic photo responses, membrane excitability, receptive‐field characteristics and morphological features. Together, the results reveal a retinal circuit that uses the sbc trigger feature to regulate irradiance coding and potentially send image‐forming cues to non‐image‐forming visual centres in the brain.
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