Centers for Disease Control and Prevention's Public Health Infrastructure Grant: A Better Approach to Empowering More State and Local Decision Making and Strengthening the Public Health Workforce and Infrastructure.

Context: In response to the COVID-19 pandemic, Congress passed the American Rescue Plan Act of 2021 (ARPA) that included a historic investment in the public health workforce.

Program: Charged with implementing this investment, the U.S.

Inner limiting Membrane Peel Extends Calcium Imaging of Retinal Ganglion Cell Activity Beyond the Fovea in Non-Human Primate.

High resolution retinal imaging paired with intravitreal injection of a viral vector coding for the calcium indicator GCaMP has enabled visualization of activity dependent calcium changes in retinal ganglion cells (RGCs) at single cell resolution in the living eye. The inner limiting membrane (ILM) is a barrier for viral vectors, restricting transduction to a ring of RGCs serving the fovea in both humans and non-human primates (NHP). We evaluate peeling the ILM prior to intravitreal injection as a strategy to expand calcium imaging beyond the fovea in the NHP eye in vivo.

Cone-Opponent Ganglion Cells in the Primate Fovea Tuned to Noncardinal Color Directions.

A long-standing question in vision science is how the three cone photoreceptor types-long (L), medium (M), and short (S) wavelength sensitive-combine to generate our perception of color. Hue perception can be described along two opponent axes: red-green and blue-yellow. Psychophysical measurements of color appearance indicate that the cone inputs to the red-green and blue-yellow opponent axes are M vs.

Synaptic Origins of the Complex Receptive Field Structure in Primate Smooth Monostratified Retinal Ganglion Cells.

Considerable progress has been made in studying the receptive fields of the most common primate retinal ganglion cell (RGC) types, such as parasol RGCs. Much less is known about the rarer primate RGC types and the circuitry that gives rise to noncanonical receptive field structures. The goal of this study was to analyze synaptic inputs to smooth monostratified RGCs to determine the origins of their complex spatial receptive fields, which contain isolated regions of high sensitivity called "hotspots.

Cone-Opponent Ganglion Cells in the Primate Fovea Tuned to Non-Cardinal Color Directions.

A long-standing question in vision science is how the three cone photoreceptor types - long (L), medium (M) and short (S) wavelength sensitive - combine to generate our perception of color. Hue perception can be described along two opponent axes: red-green and blue-yellow. Psychophysical measurements of color appearance indicate that the cone inputs to the red-green and blue-yellow opponent axes are M vs.

In vivo chromatic and spatial tuning of foveolar retinal ganglion cells in Macaca fascicularis.

The primate fovea is specialized for high acuity chromatic vision, with the highest density of cone photoreceptors and a disproportionately large representation in visual cortex. The unique visual properties conferred by the fovea are conveyed to the brain by retinal ganglion cells, the somas of which lie at the margin of the foveal pit. Microelectrode recordings of these centermost retinal ganglion cells have been challenging due to the fragility of the fovea in the excised retina.

The Developmental Progression of Eight Opsin Spectral Signals Recorded from the Zebrafish Retinal Cone Layer Is Altered by the Timing and Cell Type Expression of Thyroxin Receptor β2 (trβ2) Gain-Of-Function Transgenes.

Zebrafish retinal cone signals shift in spectral shape through larval, juvenile, and adult development as expression patterns of eight cone-opsin genes change. An algorithm extracting signal amplitudes for the component cone spectral types is developed and tested on two thyroxin receptor β2 (trβ2) gain-of-function lines and , allowing correlation between opsin signaling and opsin immunoreactivity in lines with different developmental timing and cell-type expression of this red-opsin-promoting transgene. Both adult transgenics became complete, or nearly complete, "red-cone dichromats," with disproportionately large long-wavelength-sensitive (LWS)1 opsin amplitudes as compared with controls, where LWS1 and LWS2 amplitudes were about equal, and significant signals from SWS1, SWS2, and Rh2 opsins were detected.

Synaptic inputs to displaced intrinsically-photosensitive ganglion cells in macaque retina.

Ganglion cells are the projection neurons of the retina. Intrinsically photosensitive retinal ganglion cells (ipRGCs) express the photopigment melanopsin and also receive input from rods and cones via bipolar cells and amacrine cells. In primates, multiple types of ipRGCs have been identified.

Conserved circuits for direction selectivity in the primate retina.

The detection of motion direction is a fundamental visual function and a classic model for neural computation. In the non-primate retina, direction selectivity arises in starburst amacrine cell (SAC) dendrites, which provide selective inhibition to direction-selective retinal ganglion cells (dsRGCs). Although SACs are present in primates, their connectivity and the existence of dsRGCs remain open questions.

S-cone circuits in the primate retina for non-image-forming vision.

Intrinsically photosensitive retinal ganglion cells (ipRGCs) respond directly to light by virtue of containing melanopsin which peaks at about 483 nm. However, in primates, ipRGCs also receive color opponent inputs from short-wavelength-sensitive (S) cone circuits that are well-suited to encode circadian changes in the color of the sky that accompany the rising and setting sun. Here, we review the retinal circuits that endow primate ipRGCs with the cone-opponency capable of encoding the color of the sky and contributing to the wide-ranging effects of short-wavelength light on ipRGC-mediated non-image-forming visual function in humans.

Synaptic inputs to broad thorny ganglion cells in macaque retina.

In primates, broad thorny retinal ganglion cells are highly sensitive to small, moving stimuli. They have tortuous, fine dendrites with many short, spine-like branches that occupy three contiguous strata in the middle of the inner plexiform layer. The neural circuits that generate their responses to moving stimuli are not well-understood, and that was the goal of this study.

Another Blue-ON ganglion cell in the primate retina.

A classic and highly influential model of visual processing proposes that the role of the retina is to compress visual information for optimal transmission to the brain [1]. Drawing on ideas from information theory, an efficient retinal code could be defined as one that reduces redundancy to communicate as much information as possible, given the optic nerve's limited capacity. From this redundancy reduction hypothesis, a theory of retinal color coding emerged in which the three most common retinal ganglion cell (RGC) types captured much of the variance in natural spectra [2].

Foxa1 and Foxa2 orchestrate development of the urethral tube and division of the embryonic cloaca through an autoregulatory loop with Shh.

Congenital anomalies of external genitalia affect approximately 1 in 125 live male births. Development of the genital tubercle, the precursor of the penis and clitoris, is regulated by the urethral plate epithelium, an endodermal signaling center. Signaling activity of the urethral plate is mediated by Sonic hedgehog (SHH), which coordinates outgrowth and patterning of the genital tubercle by controlling cell cycle kinetics and expression of downstream genes.

Effect of cone spectral topography on chromatic detection sensitivity.

The spatial and spectral topography of the cone mosaic set the limits for detection and discrimination of chromatic sinewave gratings. Here, we sought to compare the spatial characteristics of mechanisms mediating hue perception against those mediating chromatic detection in individuals with known spectral topography and with optical aberrations removed with adaptive optics. Chromatic detection sensitivity in general exceeded previous measurements and decreased monotonically for increasingly skewed cone spectral compositions.

A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations.

Photopigment genes, cones, and color update: disrupting the splicing code causes a diverse array of vision disorders.

The human long- and middle-wavelength sensitive cone opsin genes exhibit an extraordinary degree of haplotype diversity that results from recombination mechanisms that have intermixed the genes. As a first step in expression, genes-including the protein coding exons and intervening introns-are transcribed. Next, transcripts are spliced to remove the introns and join the exons to generate a mature message that codes for the protein.

A Color Vision Circuit for Non-Image-Forming Vision in the Primate Retina.

Melanopsin-expressing, intrinsically photosensitive retinal ganglion cells (ipRGCs) synchronize our biological clocks with the external light/dark cycle [1]. In addition to photoentrainment, they mediate the effects of light experience as a central modulator of mood, learning, and health [2]. This makes a complete account of the circuity responsible for ipRGCs' light responses essential to understanding their diverse roles in our well-being.

Wide-field amacrine cell inputs to ON parasol ganglion cells in macaque retina.

Parasol cells are one of the major types of primate retinal ganglion cells. The goal of this study was to describe the synaptic inputs that shape the light responses of the ON type of parasol cells, which are excited by increments in light intensity. A connectome from central macaque retina was generated by serial blockface scanning electron microscopy.

Cisplatin-resistant triple-negative breast cancer subtypes: multiple mechanisms of resistance.

Background: Understanding mechanisms underlying specific chemotherapeutic responses in subtypes of cancer may improve identification of treatment strategies most likely to benefit particular patients. For example, triple-negative breast cancer (TNBC) patients have variable response to the chemotherapeutic agent cisplatin. Understanding the basis of treatment response in cancer subtypes will lead to more informed decisions about selection of treatment strategies.

Strain variations in cone wavelength peaks during zebrafish development.

There are four cone morphologies in zebrafish, corresponding to UV (U), blue (B), green (G), and red (R)-sensing types; yet genetically, eight cone opsins are expressed. How eight opsins are physiologically siloed in four cone types is not well understood, and in larvae, cone physiological spectral peaks are unstudied. We use a spectral model to infer cone wavelength peaks, semisaturation irradiances, and saturation amplitudes from electroretinogram (ERG) datasets composed of multi-wavelength, multi-irradiance, aspartate-isolated, cone-PIII signals, as compiled from many 5- to 12-day larvae and 8- to 18-month-old adult eyes isolated from wild-type (WT) or roy orbison (roy) strains.

Reconciling Color Vision Models With Midget Ganglion Cell Receptive Fields.

Midget retinal ganglion cells (RGCs) make up the majority of foveal RGCs in the primate retina. The receptive fields of midget RGCs exhibit both spectral and spatial opponency and are implicated in both color and achromatic form vision, yet the exact mechanisms linking their responses to visual perception remain unclear. Efforts to develop color vision models that accurately predict all the features of human color and form vision based on midget RGCs provide a case study connecting experimental and theoretical neuroscience, drawing on diverse research areas such as anatomy, physiology, psychophysics, and computer vision.

An S-cone circuit for edge detection in the primate retina.

Midget retinal ganglion cells (RGCs) are the most common RGC type in the primate retina. Their responses have been proposed to mediate both color and spatial vision, yet the specific links between midget RGC responses and visual perception are unclear. Previous research on the dual roles of midget RGCs has focused on those comparing long (L) vs.

Synaptic inputs from identified bipolar and amacrine cells to a sparsely branched ganglion cell in rabbit retina.

There are more than 30 distinct types of mammalian retinal ganglion cells, each sensitive to different features of the visual environment. In rabbit retina, they can be grouped into four classes according to their morphology and stratification of their dendrites in the inner plexiform layer (IPL). The goal of this study was to describe the synaptic inputs to one type of Class IV ganglion cell, the third member of the sparsely branched Class IV cells (SB3).

Re-evaluation of the ethylene-dependent and -independent pathways in the regulation of floral and organ abscission.

Abscission is a developmental process with important implications for agricultural practices. Ethylene has long been considered as a key regulator of the abscission process. The existence of an ethylene-independent abscission pathway, controlled by the complex of INFLORESCENCE DEFICIENT IN ABSCISSION (IDA) peptide and the HAESA (HAE) and HAESA-like2 (HSL2) kinases, has been proposed, based mainly on observations that organ abscission in ethylene-insensitive mutants was delayed but not inhibited.

Utility of the JAX Clinical Knowledgebase in capture and assessment of complex genomic cancer data.

Cancer genomic data is continually growing in complexity, necessitating improved methods for data capture and analysis. Tumors often contain multiple therapeutically relevant alterations, and co-occurring alterations may have a different influence on therapeutic response compared to if those alterations were present alone. One clinically important example of this is the existence of a resistance conferring alteration in combination with a therapeutic sensitizing mutation.