The surface area of early visual cortices varies several fold across healthy adult humans and is genetically heritable. But the functional consequences of this anatomical variability are still largely unexplored. Here we show that interindividual variability in human visual cortical surface area reflects a tradeoff between sensitivity to visual details and susceptibility to visual context. Specifically, individuals with larger primary visual cortices can discriminate finer orientation differences, whereas individuals with smaller primary visual cortices experience stronger perceptual modulation by global orientation contexts. This anatomically correlated tradeoff between discrimination sensitivity and contextual modulation of orientation perception, however, does not generalize to contrast perception or luminance perception. Neural field simulations based on a scaling of intracortical circuits reproduce our empirical observations. Together our findings reveal a feature-specific shift in the scope of visual perception from context-oriented to detail-oriented with increased visual cortical surface area.

Orientation columns exist in the primary visual cortex (V1) of cat and primates but not mouse. Intriguingly, some recent studies reported the presence of orientation and direction columns in the mouse superficial superior colliculus (sSC), while others reported a lack of columnar organization therein. Using in vivo calcium imaging of sSC in the awake mouse brain, we found that the presence of columns is highly stimulus dependent. Specifically, we observed orientation and direction columns formed by sSC neurons retinotopically mapped to the edge of grating stimuli. For both excitatory and inhibitory neurons in sSC, orientation selectivity can be induced by the edge with their preferred orientation perpendicular to the edge orientation. Furthermore, we found that this edge-induced orientation selectivity is associated with saliency encoding. These findings indicate that the tuning properties of sSC neurons are not fixed by circuit architecture but rather dependent on the spatiotemporal properties of the stimulus.

The mineralized collagen fibril is the basic building block of bone, and is commonly pictured as a parallel array of ultrathin carbonated hydroxyapatite (HAp) platelets distributed throughout the collagen. This orientation is often attributed to an epitaxial relationship between the HAp and collagen molecules inside 2D voids within the fibril. Although recent studies have questioned this model, the structural relationship between the collagen matrix and HAp, and the mechanisms by which collagen directs mineralization remain unclear. Here, we use XRD to reveal that the voids in the collagen are in fact cylindrical pores with diameters of ~2 nm, while electron microscopy shows that the HAp crystals in bone are only uniaxially oriented with respect to the collagen. From in vitro mineralization studies with HAp, CaCO3 and γ-FeOOH we conclude that confinement within these pores, together with the anisotropic growth of HAp, dictates the orientation of HAp crystals within the collagen fibril.

Sensory neurons downstream of primary receptors are selective for specific stimulus features, and they derive their selectivity both from excitatory and inhibitory synaptic inputs from other neurons and from their own intrinsic properties. Electrical synapses, formed by gap junctions, modulate sensory circuits. Retinal ganglion cells (RGCs) are diverse feature detectors carrying visual information to the brain, and receive excitatory input from bipolar cells and inhibitory input from amacrine cells (ACs). Here we describe a RGC that relies on gap junctions, rather than chemical synapses, to convey its selectivity for the orientation of a visual stimulus. This represents both a new functional role of electrical synapses as the primary drivers of feature selectivity and a new circuit mechanism for orientation selectivity in the retina.

Despite the growing evidence for the regulated spindle orientation in mammals, a systematic approach for identifying the responsible genes in mammalian cells has not been established. Here we perform a kinase-targeting RNAi screen in HeLa cells and identify ABL1 as a novel regulator of spindle orientation. Knockdown of ABL1 causes the cortical accumulation of Leu-Gly-Asn repeat-enriched-protein (LGN), an evolutionarily conserved regulator of spindle orientation. This results in the LGN-dependent spindle rotation and spindle misorientation. In vivo inactivation of ABL1 by a pharmacological inhibitor or by ablation of the abl1 gene causes spindle misorientation and LGN mislocalization in mouse epidermis. Furthermore, ABL1 directly phosphorylates NuMA, a binding partner of LGN, on tyrosine 1774. This phosphorylation maintains the cortical localization of NuMA during metaphase, and ensures the LGN/NuMA-dependent spindle orientation control. This study provides a novel approach to identify genes regulating spindle orientation in mammals and uncovers new signalling pathways for this mechanism.

Hair cells detect sound, head position or water movements when their mechanosensory hair bundle is deflected. Each hair bundle has an asymmetric architecture that restricts stimulus detection to a single axis. Coordinated hair cell orientations within sensory epithelia further tune stimulus detection at the organ level. Here, we identify GPR156, an orphan GPCR of unknown function, as a critical regulator of hair cell orientation. We demonstrate that the transcription factor EMX2 polarizes GPR156 distribution, enabling it to signal through Gαi and trigger a 180° reversal in hair cell orientation. GPR156-Gαi mediated reversal is essential to establish hair cells with mirror-image orientations in mouse otolith organs in the vestibular system and in zebrafish lateral line. Remarkably, GPR156-Gαi also instructs hair cell reversal in the auditory epithelium, despite a lack of mirror-image organization. Overall, our work demonstrates that conserved GPR156-Gαi signaling is integral to the framework that builds directional responses into mechanosensory epithelia.

Preneoplastic mammary tissues from human female BRCA1 mutation carriers, or Brca1-mutant mice, display unexplained abnormalities in luminal differentiation. We now study the division characteristics of human mammary cells purified from female BRCA1 mutation carriers or non-carrier donors. We show primary BRCA1 mutant/+ cells exhibit defective BRCA1 localization, high radiosensitivity and an accelerated entry into cell division, but fail to orient their cell division axis. We also analyse 15 genetically-edited BRCA1 mutant/+ human mammary cell-lines and find that cells carrying pathogenic BRCA1 mutations acquire an analogous defect in their division axis accompanied by deficient expression of features of mature luminal cells. Importantly, these alterations are independent of accumulated DNA damage, and specifically dependent on elevated PLK1 activity induced by reduced BRCA1 function. This essential PLK1-mediated role of BRCA1 in controlling the cell division axis provides insight into the phenotypes expressed during BRCA1 tumorigenesis.

Inputs from the two eyes are first combined in simple cells in the primary visual cortex. Consequently, visual cortical neurons need to have the flexibility to encode visual features under both monocular and binocular situations. Here we show that binocular orientation selectivity of mouse simple cells is nearly identical to monocular orientation selectivity in both anaesthetized and awake conditions. In vivo whole-cell recordings reveal that the binocular integration of membrane potential responses is sublinear. The sublinear integration keeps binocularly evoked depolarizations below threshold at non-preferred orientations, thus preserving orientation selectivity. Computational simulations based on measured synaptic conductances indicate that inhibition promotes sublinear binocular integration, which are further confirmed by experiments using genetic and pharmacological manipulations. Our findings therefore reveal a cellular mechanism for how visual system can switch effortlessly between monocular and binocular conditions. The same mechanism may apply to other sensory systems that also integrate multiple channels of inputs.

A state of matter in which molecules show a long-range orientational order and no positional order is called a nematic liquid crystal. The best known and most widely used (for example, in modern displays) is the uniaxial nematic, with the rod-like molecules aligned along a single axis, called the director. When the molecules are chiral, the director twists in space, drawing a right-angle helicoid and remaining perpendicular to the helix axis; the structure is called a chiral nematic. Here using transmission electron and optical microscopy, we experimentally demonstrate a new nematic order, formed by achiral molecules, in which the director follows an oblique helicoid, maintaining a constant oblique angle with the helix axis and experiencing twist and bend. The oblique helicoids have a nanoscale pitch. The new twist-bend nematic represents a structural link between the uniaxial nematic (no tilt) and a chiral nematic (helicoids with right-angle tilt).

Control of spindle orientation is a fundamental process for embryonic development, morphogenesis and tissue homeostasis, while defects are associated with tumorigenesis and other diseases. Force sensing is one of the mechanisms through which division orientation is determined. Here we show that integrin β1 plays a critical role in this process, becoming activated at the lateral regions of the cell cortex in a ligand-independent manner. This activation is force dependent and polar, correlating with the spindle capture sites. Inhibition of integrin β1 activation on the cortex and disruption of its asymmetric distribution leads to spindle misorientation, even when cell adhesion is β1 independent. Examining downstream targets reveals that a cortical mechanosensory complex forms on active β1, and regulates spindle orientation irrespective of cell context. We propose that ligand-independent integrin β1 activation is a conserved mechanism that allows cell responses to external stimuli.

There is great interest in exploiting van der Waals gaps in layered materials as nanofluidic channels. Graphene oxide (GO) nanosheets are known to spontaneously assemble into stacked planar membranes with transport properties that are highly selective to molecular structure. Use of conventional GO membranes in liquid-phase applications is often limited by low flux values, due to intersheet nanochannel alignment perpendicular to the desired Z-directional transport, which leads to circuitous fluid pathways that are orders of magnitude longer than the membrane thickness. Here we demonstrate an approach that uses compressive instability in Zr-doped GO thin films to create wrinkle patterns that rotate nanosheets to high angles. Capturing this structure in polymer matrices and thin sectioning produce fully dense membranes with arrays of near-vertically aligned nanochannels. These robust nanofluidic devices offer pronounced reduction in fluid path-length, while retaining the high selectivity for water over non-polar molecules characteristic of GO interlayer nanochannels.

Non-destructive orientation mapping is an important characterization tool in materials science and geoscience for understanding and/or improving material properties based on their grain structure. Confocal Raman microscopy is a powerful non-destructive technique for chemical mapping of organic and inorganic materials. Here we demonstrate orientation mapping by means of Polarized Raman Microscopy (PRM). While the concept that PRM is sensitive to orientation changes is known, to our knowledge, an actual quantitative orientation mapping has never been presented before. Using a concept of ambiguity-free orientation determination analysis, we present fast and quantitative single-acquisition Raman-based orientation mapping by simultaneous registration of multiple Raman scattering spectra obtained at different polarizations. We demonstrate applications of this approach for two- and three-dimensional orientation mapping of a multigrain semiconductor, a pharmaceutical tablet formulation and a polycrystalline sapphire sample. This technique can potentially move traditional X-ray and electron diffraction type experiments into conventional optical laboratories.

Maintaining spatial orientation when carrying out goal-directed movements requires an animal to perform angular path integration. Such functionality has been recently demonstrated in the ellipsoid body (EB) of fruit flies, though the precise circuitry and underlying mechanisms remain unclear. We analyze recently published cellular-level connectomic data and identify the unique characteristics of the EB circuitry, which features coupled symmetric and asymmetric rings. By constructing a spiking neural circuit model based on the connectome, we reveal that the symmetric ring initiates a feedback circuit that sustains persistent neural activity to encode information regarding spatial orientation, while the asymmetric rings are capable of integrating the angular path when the body rotates in the dark. The present model reproduces several key features of EB activity and makes experimentally testable predictions, providing new insight into how spatial orientation is maintained and tracked at the cellular level.Ellipsoid body (EB) neurons in the fruit fly represent the animal heading through a bump-like activity dynamics. Here the authors report a connectome-driven spiking neural circuit model of the EB and the protocerebral bridge (PB) that can maintain and update an activity bump related to the spatial orientation.

Polymer chains are attached to nanoparticle surfaces for many purposes, including altering solubility, influencing aggregation, dispersion, and even tailoring immune responses in drug delivery. The most unique structural motif of polymer-grafted nanoparticles (PGNs) is the high-density region in the corona where polymer chains are stretched under significant confinement, but orientation of these chains has never been measured because conventional nanoscale-resolved measurements lack sensitivity to polymer orientation in amorphous regions. Here, we directly measure local chain orientation in polystyrene grafted gold nanoparticles using polarized resonant soft X-ray scattering (P-RSoXS). Using a computational scattering pattern simulation approach, we measure the thickness of the anisotropic region of the corona and extent of chain orientation within it. These results demonstrate the power of P-RSoXS to discover and quantify orientational aspects of structure in amorphous soft materials and provide a framework for applying this emerging technique to more complex, chemically heterogeneous systems in the future.

PROteolysis-TArgeting Chimeras (PROTACs) are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted degradation. Many potent PROTACs with specificity for dissimilar targets have been developed; however, the factors governing degradation selectivity within closely-related protein families remain elusive. Here, we generate isoform-selective PROTACs for the p38 MAPK family using a single warhead (foretinib) and recruited E3 ligase (von Hippel-Lindau). Based on their distinct linker attachments and lengths, these two PROTACs differentially recruit VHL, resulting in degradation of p38α or p38δ. We characterize the role of ternary complex formation in driving selectivity, showing that it is necessary, but insufficient, for PROTAC-induced substrate ubiquitination. Lastly, we explore the p38δ:PROTAC:VHL complex to explain the different selectivity profiles of these PROTACs. Our work attributes the selective degradation of two closely-related proteins using the same warhead and E3 ligase to heretofore underappreciated aspects of the ternary complex model.

Sub-10 nm patterns prepared by directed self-assembly (DSA) of block copolymer (BCP) thin films offer a breakthrough method to overcome the limitations of photolithography. Perpendicular orientation of the BCP nanostructures is essential for lithographic applications, but dissimilar surface/interfacial energies of two blocks generally favour parallel orientations, so that the perpendicular orientation could only be obtained under very limited conditions. Here, we introduce a generalized method for creating perpendicular orientations by filtered plasma treatment of the BCP films. By cross-linking the surface of disordered BCP films using only physical collisions of neutral species without ion bombardment or UV irradiation, neutral layers consistent with the BCP volume fraction are produced that promote the perpendicular orientations. This method works with BCPs of various types, volume fractions, and molecular weights individually at the top and bottom interfaces, so it was applied to orientation-controlled 3D multilayer structures and DSA processes for sub-10 nm line-spacing patterns.

The orientation of luminescent molecules in organic light-emitting diodes strongly influences device performance. However, our understanding of the factors controlling emitter orientation is limited as current measurements only provide ensemble-averaged orientation values. Here, we use single-molecule imaging to measure the transition dipole orientation of individual emitter molecules in a state-of-the-art thermally evaporated host and thereby obtain complete orientation distributions of the hyperfluorescence-terminal emitter C545T. We achieve this by realizing ultra-low doping concentrations (10-6 wt%) of C545T and minimising background levels to reliably measure its photoluminescence. This approach yields the orientation distributions of >1000 individual emitter molecules in a system relevant to vacuum-processed devices. Analysis of solution- and vacuum-processed systems reveals that the orientation distributions strongly depend on the nanoscale environment of the emitter. This work opens the door to attaining unprecedented information on the factors that determine emitter orientation in current and future material systems for organic light-emitting devices.

Orientation selectivity in primate visual cortex is organized into cortical columns. Since cortical columns are at a finer spatial scale than the sampling resolution of standard BOLD fMRI measurements, analysis approaches have been proposed to peer past these spatial resolution limitations. It was recently found that these methods are predominantly sensitive to stimulus vignetting - a form of selectivity arising from an interaction of the oriented stimulus with the aperture edge. Beyond vignetting, it is not clear whether orientation-selective neural responses are detectable in BOLD measurements. Here, we leverage a dataset of visual cortical responses measured using high-field 7T fMRI. Fitting these responses using image-computable models, we compensate for vignetting and nonetheless find reliable tuning for orientation. Results further reveal a coarse-scale map of orientation preference that may constitute the neural basis for known perceptual anisotropies. These findings settle a long-standing debate in human neuroscience, and provide insights into functional organization principles of visual cortex.

Sensory systems face a barrage of stimulation that continually changes along multiple dimensions. These simultaneous changes create a formidable problem for the nervous system, as neurons must dynamically encode each stimulus dimension, despite changes in other dimensions. Here, we measured how neurons in visual cortex encode orientation following changes in luminance and contrast, which are critical for visual processing, but nuisance variables in the context of orientation coding. Using information theoretic analysis and population decoding approaches, we find that orientation discriminability is luminance and contrast dependent, changing over time due to firing rate adaptation. We also show that orientation discrimination in human observers changes during adaptation, in a manner consistent with the neuronal data. Our results suggest that adaptation does not maintain information rates per se, but instead acts to keep sensory systems operating within the limited dynamic range afforded by spiking activity, despite a wide range of possible inputs.

Estimating the orientation and 3D position of rotationally constrained emitters with localization microscopy typically requires polarization splitting or a large engineered Point Spread Function (PSF). Here we utilize a compact modified PSF for single molecule emitter imaging to estimate simultaneously the 3D position, dipole orientation, and degree of rotational constraint from a single 2D image. We use an affordable and commonly available phase plate, normally used for STED microscopy in the excitation light path, to alter the PSF in the emission light path. This resulting Vortex PSF does not require polarization splitting and has a compact PSF size, making it easy to implement and combine with localization microscopy techniques. In addition to a vectorial PSF fitting routine we calibrate for field-dependent aberrations which enables orientation and position estimation within 30% of the Cramér-Rao bound limit over a 66 μm field of view. We demonstrate this technique on reorienting single molecules adhered to the cover slip, λ-DNA with DNA intercalators using binding-activated localization microscopy, and we reveal periodicity on intertwined structures on supercoiled DNA.