Biology subjects

Naka, A.

Publications and source records attributed to Naka, A..

4 recordsLinked to original sources

bioRxiv2025

WAChRs are excitatory opsins sensitive to indoor lighting

Hundreds of novel opsins have been characterized since the advent of optogenetics, but low experimental throughput has limited the scale of opsin engineering campaigns. We modified an automated patch-clamp system with a multispectral light source and a custom light path to enable high-throughput electrophysiological measurements of opsin functional properties. Using this approach, we screened over 1,750 opsins from a range of families. We discovered that the F240A mutation of the light-gated potassium channel WiChR abolished potassium selectivity, turning it into a sensitive excitatory channel that we dubbed "WAChR". We systematically mutated WAChR and identified variants that expand the frontier of speed-sensitivity tradeoffs. Multiple WAChR variants produced large inward currents in response to indoor ambient office light, and responded to irradiances as low as 15 nW/mm2, something that we did not observe with other ultra-sensitive opsins. In vivo recording from the mouse cortex confirmed that WAChRs exhibit enhanced sensitivity in neurons. These ambient-light sensitive channels should be broadly useful for neuroscience research and vision restoration therapies.

neuroscience↗

bioRxiv2025

Crowdsourced Protein Design: Lessons From the Adaptyv EGFR Binder Competition

In this report, we summarize and analyze the 2024 Adaptyv protein design competition. Participants used computational and Machine Learning (ML) methods of their choice to design proteins that bind the Epidermal Growth Factor Receptor (EGFR), a key drug target involved in cell growth, differentiation, and cancer development. Over 1,800 designs were submitted across two rounds. Of these, 601 proteins were selected and characterized for expression and binding affinity to EGFR, with competitors both optimizing existing binders (KD = 1.21 nM) and creating de novo binders (KD = 82 nM). All selected designs were experimentally validated using Adaptyvs automated Bio-Layer Interferometry (BLI) pipeline. This competition illustrates the potential of crowdsourcing to drive creativity and innovation in protein design. However, it also exposed key challenges, such as the lack of standardized benchmarks, experimental design targets, and robust computational metrics for method comparison. We anticipate that future competitions will address these gaps and further motivate progress in computational protein design.

bioengineering↗

bioRxiv2022

Evaluating instruments for assessing healthspan: a multi-center cross-sectional study on health-related quality of life (HRQL) and frailty in the companion dog

Developing valid tools that assess key determinants of canine healthspan such as frailty and health-related quality of life (HRQL) is essential to characterizing and understanding aging in dogs. Additionally, because the companion dog is an excellent translational model for humans, such tools can be applied to evaluate gerotherapeutics and investigate mechanisms underlying longevity in both dogs and humans. In this multi-center, cross sectional study, we investigated the use of a clinical questionnaire (Canine Frailty Index; CFI; Banzato et al., 2019) to assess frailty and an owner assessment tool (VetMetrica HRQL) to evaluate HRQL in 451 adult companion dogs. Results demonstrated validity of the tools by confirming expectations that frailty and HRQL deteriorate with age. CFI scores were significantly higher (higher frailty) and HRQL scores significantly lower (worse HRQL) in old dogs ([≥] 7 years of age) compared to young dogs ([≥] 2 and < 6 years of age). Body size (small < 25lbs or large > 50lbs) was not associated with CFI or total HRQL score. However, older, larger dogs showed faster age-related decline in HRQL scores specific to owner-reported activity and comfort. Findings suggest that the clinician-assessed CFI and owner-reported VetMetrica HRQL are useful tools to evaluate two determinants of healthspan in dogs: the accumulation of frailty and the progressive decline in quality of life. Establishing validated tools that operationalize the assessment of canine healthspan is critical for the advancement of geroscience and the development of gerotherapeutics that benefit both human and veterinary medicine. Graphical abstractGraphical summary of the design, results, and conclusions of the study. O_FIG O_LINKSMALLFIG WIDTH=179 HEIGHT=200 SRC="FIGDIR/small/500746v1_ufig1.gif" ALT="Figure 1"> View larger version (41K): org.highwire.dtl.DTLVardef@1d70950org.highwire.dtl.DTLVardef@a4748borg.highwire.dtl.DTLVardef@df6892org.highwire.dtl.DTLVardef@14a7aed_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2018

Complementary subnetworks of cortical somatostatin interneurons

The neocortex is organized into discrete layers of excitatory neurons: layer 4 receives the densest bottom up projection carrying external sensory data, while layers 2/3 and 5 receive top down inputs from higher cortical areas that may convey sensory expectations and behavioral goals. A subset of cortical somatostatin (SST) neurons gate top down input and control sensory computation by inhibiting the apical dendrites of pyramidal cells in layers 2/3 and 5. However, it is unknown whether an analogous inhibitory mechanism separately and specifically controls activity in layer 4. We hypothesized that distinct SST circuits might exist to inhibit specific cortical layers. By enforcing layer-specific inhibition, distinct SST subnetworks could mediate pathway-specific gain control, such as regulating the balance between bottom up and top down input. Employing a combination of high precision circuit mapping, in vivo optogenetic perturbations, and single cell transcriptional profiling, we reveal distinct and complementary SST circuits that specifically and reciprocally interconnect with excitatory cells in either layer 4 or layers 2/3 and 5. Our data further define a transcriptionally distinct SST neuronal sub-class that powerfully gates bottom up sensory activity during active sensation by regulating layer 4 activity. This integrated paradigm further represents a potentially generalizable approach to identify and characterize neuronal cell types and reveal their in vivo function.

neuroscience↗