Conditioned inhibition and reinforcement rate

We investigated conditioned inhibition in a magazine approach paradigm. Rats were trained on a feature negative discrimination between an auditory conditioned stimulus (CS) reinforced at one rate versus a compound of that CS and a visual stimulus (L) reinforced at a lower rate. This training established L as a conditioned inhibitor. We then tested the inhibitory strength of L by presenting it in compound with other auditory CSs. L reduced responding when tested with a CS that had been reinforced at a high rate, but had less or even no inhibitory effect when tested with a CS that had been reinforced at a low rate. The inhibitory strength of L was greater if it signaled a decrease in reinforcement from an already low rate than if it signaled an equivalent decrease in reinforcement from a high rate. We conclude that the strength of inhibition is not a linear function of the change in reinforcement that it signals. We discuss the implications of this finding for models of learning (e.g. Rescorla & Wagner, 1972) that identify inhibition with a difference (subtraction) rule.Australian Research Counci

Magazine approach during a signal for food depends on Pavlovian, not instrumental, conditioning

In the conditioned magazine approach paradigm, rats are exposed to a contingent relationship between a conditioned stimulus (CS) and the delivery of food (the unconditioned stimulus, US). As the rats learn the CS-US association, they make frequent anticipatory head entries into the food magazine (the conditioned response, CR) during the CS. Conventionally, this is considered to be a Pavlovian paradigm because food is contingent on the CS and not on the performance of CRs during the CS. However, because magazine entries during the CS are reliably followed by food, the increase in frequency of those responses may involve adventitious (“superstitious”) instrumental conditioning. The existing evidence, from experiments using an omission schedule to eliminate the possibility of instrumental conditioning (Farwell & Ayres, 1979; Holland, 1979), is ambiguous: rats acquire magazine CRs despite the omission schedule, demonstrating that the response does not depend on instrumental conditioning, but the response rate is greatly depressed compared with that of rats trained on a yoked schedule, consistent with a contribution from instrumental conditioning under normal (non-omission) schedules. Here we describe experiments in which rats were trained on feature-positive or feature-negative type discriminations between trials that were reinforced on an omission schedule versus trials reinforced on a yoked schedule. The experiments show that the difference in responding between omission and yoked schedules is due to suppression of responding under the omission schedule rather than an elevation of responding under the yoked schedule. We conclude that magazine responses during the CS are largely or entirely Pavlovian CRs.Australian Research Council: Grant DP109269

Erratum to: Genetic alterations of m6A regulators predict poorer survival in acute myeloid leukemia

Abstract Methylation of N6 adenosine (m6A) is known to be important for diverse biological processes including gene expression control, translation of protein, and messenger RNA (mRNA) splicing. However, its role in the development of human cancers is poorly understood. By analyzing datasets from the Cancer Genome Atlas Research Network (TCGA) acute myeloid leukemia (AML) study, we discover that mutations and/or copy number variations of m6A regulatory genes are strongly associated with the presence of TP53 mutations in AML patients. Further, our analyses reveal that alterations in m6A regulatory genes confer a worse survival in AML. Our work indicates that genetic alterations of m6A regulatory genes may cooperate with TP53 and/or its regulator/downstream targets in the pathogenesis and/or maintenance of AML

Chiral emergence in multistep hierarchical assembly of achiral conjugated polymers

Intimately connected to the rule of life, chirality remains a long-time fascination in biology, chemistry, physics and materials science. Chiral structures, e.g., nucleic acid and cholesteric phase developed from chiral molecules are common in nature and synthetic soft materials. While it was recently discovered that achiral but bent core mesogens can also form chiral helices, the assembly of chiral microstructures from achiral polymers has rarely been explored. Here, we reveal chiral emergence from achiral conjugated polymers for the first time, in which hierarchical helical structures are developed through a multistep assembly pathway. Upon increasing concentration beyond a threshold volume fraction, pre-aggregated polymer nanofibers form lyotropic liquid crystalline (LC) mesophases with complex, chiral morphologies. Combining imaging, X-ray and spectroscopy techniques with molecular simulations, we demonstrate that this structural evolution arises from torsional polymer molecules which induce multiscale helical assembly, progressing from nano- to micron scale helical structures as the solution concentration increases. This study unveils a previously unknown complex state of matter for conjugated polymers that can pave way to a new field of chiral (opto)electronics. We anticipate that hierarchical chiral helical structures can profoundly impact how conjugated polymers interact with light, transport charges, and transduce signals from biomolecular interactions and even give rise to properties unimagined before.Comment: 47 pages, 7 figure

Fluctuations and Intrinsic Pinning in Layered Superconductors

A flux liquid can condense into a smectic crystal in a pure layered superconductors with the magnetic field oriented nearly parallel to the layers. If the smectic order is commensurate with the layering, this crystal is {\sl stable} to point disorder. By tilting and adjusting the magnitude of the applied field, both incommensurate and tilted smectic and crystalline phases are found. We discuss transport near the second order smectic freezing transition, and show that permeation modes lead to a small non--zero resistivity and large but finite tilt modulus in the smectic crystal.Comment: 4 pages + 1 style file + 1 figure (as uufile) appended, REVTEX 3.

Macrophage development and activation involve coordinated intron retention in key inflammatory regulators

Monocytes and macrophages are essential components of the innate immune system. Herein, we report that intron retention (IR) plays an important role in the development and function of these cells. Using Illumina mRNA sequencing, Nanopore direct cDNA sequencing and proteomics analysis, we identify IR events that affect the expression of key genes/proteins involved in macrophage development and function. We demonstrate that decreased IR in nuclear-detained mRNA is coupled with increased expression of genes encoding regulators of macrophage transcription, phagocytosis and inflammatory signalling, including ID2, IRF7, ENG and LAT. We further show that this dynamic IR program persists during the polarisation of resting macrophages into activated macrophages. In the presence of proinflammatory stimuli, intron-retaining CXCL2 and NFKBIZ transcripts are rapidly spliced, enabling timely expression of these key inflammatory regulators by macrophages. Our study provides novel insights into the molecular factors controlling vital regulators of the innate immune response

Switchable X-ray Orbital Angular Momentum from an Artificial Spin Ice

Artificial spin ices (ASI) have been widely investigated as magnetic metamaterials with exotic properties governed by their geometries. In parallel, interest in X-ray photon orbital angular momentum (OAM) has been rapidly growing. Here we show that a square ASI with a programmed topological defect, a double edge dislocation, imparts OAM to scattered X-rays. Unlike single dislocations, a double dislocation does not introduce magnetic frustration, and the ASI equilibrates to its antiferromagnetic (AF) ground state. The topological charge of the defect differs with respect to the structural and magnetic order; thus, X-ray diffraction from the ASI produces photons with even and odd OAM quantum numbers at the structural and AF Bragg conditions, respectively. The magnetic transitions of the ASI allow the AF OAM beams to be switched on and off by modest variations of temperature and applied magnetic field. These results demonstrate ASIs can serve as metasurfaces for reconfigurable X-ray optics that could enable selective probes of electronic and magnetic properties.Comment: 7 pages, 4 figure

Moving glass theory of driven lattices with disorder

We study periodic structures, such as vortex lattices, moving in a random potential. As predicted in [T. Giamarchi, P. Le Doussal Phys. Rev. Lett. 76 3408 (1996)] the periodicity in the direction transverse to motion leads to a new class of driven systems: the Moving Glasses. We analyse using several RG techniques the properties at T=0 and $T>0$: (i) decay of translational long range order (ii) particles flow along static channels (iii) the channel pattern is highly correlated (iv) barriers to transverse motion. We demonstrate the existence of the ``transverse critical force'' at T=0. A ``static random force'' is shown to be generated by motion. Displacements grow logarithmically in $d=3$ and algebraically in $d=2$. The persistence of quasi long range translational order in $d=3$ at weak disorder, or large velocity leads to predict a topologically ordered ``Moving Bragg Glass''. This state continues the static Bragg glass and is stable at $T>0$, with non linear transverse response and linear asymptotic behavior. In $d=2$, or in $d=3$ at intermediate disorder, another moving glass exist (the Moving Transverse Glass) with smectic quasi order in the transverse direction. A phase diagram in $T$ force and disorder for static and moving structures is proposed. For correlated disorder we predict a ``moving Bose glass'' state with anisotropic transverse Meissner effect and transverse pinning. We discuss experimental consequences such as anomalous Hall effect in Wigner crystal and transverse critical current in vortex lattice.Comment: 74 pages, 27 figures, RevTe