Trichromacy and ultraviolet vision in a nocturnal marsupial.

Color vision among mammals is diverse and complex, with many physiological and genetic factors affecting spectral sensitivity, the ability to perceive different wavelengths of light. In this study, the color vision of the sugar glider (Petaurus breviceps), a nocturnal, gliding mammal, was examined through a series of behavioral tests, genetic analyses, and immunohistochemistry. This is the first study to classify the color vision capabilities of this species.

Cooperative agreement between countries of the North Atlantic Ocean reduces marine plastic pollution but with unequal economic benefits.

Plastic pollution in the world's oceans threatens ecosystems and biodiversity. The connected nature of the marine environment suggests that coordinated actions by countries sharing an ocean border may provide more effective pollution control than unilateral actions by any one country. However, countries often fail to cooperate, even when joint economic benefits would be higher under cooperation.

Spatially resolved transcriptomics reveal the determinants of primary resistance to immunotherapy in NSCLC with mature tertiary lymphoid structures.

Effectiveness of immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) has been linked to the presence of mature tertiary lymphoid structures (mTLSs) within the tumor microenvironment (TME). However, only a subset of mTLS-positive NSCLC derives benefit, thus highlighting the need to unravel ICI response determinants. The comprehensive analysis of ICI-treated patients with NSCLC (n = 509) from the Bergonié Institute Profiling (BIP) study (NCT02534649) reveals that the presence of mTLSs correlates with improved clinical outcomes, independently of programmed death ligand 1 (PD-L1) expression and genomic features.

Different PD-L1 Assays Reveal Distinct Immunobiology and Clinical Outcomes in Urothelial Cancer.

Testing for PD-L1 expression by IHC is used to predict immune checkpoint blockade (ICB) benefits but has performed inconsistently in urothelial cancer clinical trials. Different approaches are used for PD-L1 IHC. We analyzed paired PD-L1 IHC data on urothelial cancer samples using the SP142 and 22C3 assays from the phase III IMvigor130 trial and found discordant findings summarized by four phenotypes: PD-L1 positive by both assays, PD-L1 positive by the SP142 assay only, PD-L1 positive by the 22C3 assay only, and PD-L1 negative by both assays double negative.

Cellular component transfer between photoreceptor cells of the retina.

Photoreceptor transplantation is a potential therapeutic strategy for degenerative retinal diseases. Studies on mechanisms contributing to retinal regeneration and vision repair identified cellular components transfer (CCT) as playing a role, in addition to somatic augmentation (referred to as "cell replacement" in this paper). In CCT, donor photoreceptors shuttle proteins, RNA, and mitochondria to host photoreceptors through intercellular connections.

Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma.

Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers.

The Exonuclease TREX1 Constitutes an Innate Immune Checkpoint Limiting cGAS/STING-Mediated Antitumor Immunity.

The DNA exonuclease three-prime repair exonuclease 1 (TREX1) is critical for preventing autoimmunity in mice and humans by degrading endogenous cytosolic DNA, which otherwise triggers activation of the innate cGAS/STING pathway leading to the production of type I IFNs. As tumor cells are prone to aberrant cytosolic DNA accumulation, we hypothesized that they are critically dependent on TREX1 activity to limit their immunogenicity. Here, we show that in tumor cells, TREX1 restricts spontaneous activation of the cGAS/STING pathway, and the subsequent induction of a type I IFN response.

Transcriptional priming and chromatin regulation during stochastic cell fate specification.

Stochastic cell fate specification, in which a cell chooses between two or more fates with a set probability, diversifies cell subtypes in development. Although this is a vital process across species, a common mechanism for these cell fate decisions remains elusive. This review examines two well-characterized stochastic cell fate decisions to identify commonalities between their developmental programmes.

Anti-TIGIT antibody improves PD-L1 blockade through myeloid and T cells.

Tiragolumab, an anti-TIGIT antibody with an active IgG1κ Fc, demonstrated improved outcomes in the phase 2 CITYSCAPE trial (ClinicalTrials.gov: NCT03563716 ) when combined with atezolizumab (anti-PD-L1) versus atezolizumab alone. However, there remains little consensus on the mechanism(s) of response with this combination.

Retinoic acid signaling regulates spatiotemporal specification of human green and red cones.

Trichromacy is unique to primates among placental mammals, enabled by blue (short/S), green (medium/M), and red (long/L) cones. In humans, great apes, and Old World monkeys, cones make a poorly understood choice between M and L cone subtype fates. To determine mechanisms specifying M and L cones, we developed an approach to visualize expression of the highly similar M- and L-opsin mRNAs.

Hydro-bio-geo-socio-chemical interactions and the sustainability of residential landscapes.

Residential landscapes are essential to the sustainability of large areas of the United States. However, spatial and temporal variation across multiple domains complicates developing policies to balance these systems' environmental, economic, and equity dimensions. We conducted multidisciplinary studies in the Baltimore, MD, USA, metropolitan area to identify locations (hotspots) or times (hot moments) with a disproportionate influence on nitrogen export, a widespread environmental concern.

Biophysical Measures to Support Analysis and Communication of Existence Values.

A recent focus of ecosystem services research has been on the definition of biophysical outcomes and measures most closely linked to social welfare. There is a particular need to identify biophysical outcomes corresponding to existence values. (Values associated with existence apart from any current or future use).

Spatial dimensions of water quality value in New England river networks.

Households' willingness to pay (WTP) for water quality improvements-representing their economic value-depends on where improvements occur. Households often hold higher values for improvements close to their homes or iconic areas. Are there other areas where improvements might hold high value to individual households, do effects on WTP vary by type of improvement, and can these areas be identified even if they are not anticipated by researchers? To answer these questions, we integrated a water quality model and map-based, interactive choice experiment to estimate households' WTP for water quality improvements throughout a river network covering six New England states.

Activating and repressing gene expression between chromosomes during stochastic fate specification.

DNA elements act across long genomic distances to regulate gene expression. During transvection in Drosophila, DNA elements on one allele of a gene act between chromosomes to regulate expression of the other allele. Little is known about the biological roles and developmental regulation of transvection.

The evolutionary history and spectral tuning of vertebrate visual opsins.

Many animals depend on the sense of vision for survival. In eumetazoans, vision requires specialized, light-sensitive cells called photoreceptors. Light reaches the photoreceptors and triggers the excitation of light-detecting proteins called opsins.

The diversity of invertebrate visual opsins spanning Protostomia, Deuterostomia, and Cnidaria.

Across eumetazoans, the ability to perceive and respond to visual stimuli is largely mediated by opsins, a family of proteins belonging to the G protein-coupled receptor (GPCR) superclass. Lineage-specific gains and losses led to a striking diversity in the numbers, types, and spectral sensitivities conferred by visual opsin gene expression. Here, we review the diversity of visual opsins and differences in opsin gene expression from well-studied protostome, invertebrate deuterostome, and cnidarian groups.

Temporally dynamic antagonism between transcription and chromatin compaction controls stochastic photoreceptor specification in flies.

Stochastic mechanisms diversify cell fates during development. How cells randomly choose between two or more fates remains poorly understood. In the Drosophila eye, the random mosaic of two R7 photoreceptor subtypes is determined by expression of the transcription factor Spineless (Ss).

Patterning and Development of Photoreceptors in the Human Retina.

Humans rely on visual cues to navigate the world around them. Vision begins with the detection of light by photoreceptor cells in the retina, a light-sensitive tissue located at the back of the eye. Photoreceptor types are defined by morphology, gene expression, light sensitivity, and function.

CRISPR Generated SIX6 and POU4F2 Reporters Allow Identification of Brain and Optic Transcriptional Differences in Human PSC-Derived Organoids.

Human pluripotent stem cells (PSCs) represent a powerful tool to investigate human eye development and disease. When grown in 3D, they can self-assemble into laminar organized retinas; however, variation in the size, shape and composition of individual organoids exists. Neither the microenvironment nor the timing of critical growth factors driving retinogenesis are fully understood.

Transcriptional repression in stochastic gene expression, patterning, and cell fate specification.

Development is often driven by signaling and lineage-specific cues, yielding highly uniform and reproducible outcomes. Development also involves mechanisms that generate noise in gene expression and random patterns across tissues. Cells sometimes randomly choose between two or more cell fates in a mechanism called stochastic cell fate specification.