Inactivation of Basolateral Amygdala Specifically Eliminates Palatability-Related Information in Cortical Sensory Responses

Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)—anatomically interconnected nodes of the gustatory system—code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through “epochs.” The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during, and after temporarily inactivating BLA in awake rats. BLA inactivation (BLAx) changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste specificity of responses remained stable; information about taste palatability, however, which normally resides in the “Late” epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity. Evidence indirectly implicates the amygdala as the primary processor of emotional information used by cortex to drive appropriate behavioral responses to stimuli. Taste provides an ideal system with which to test this hypothesis directly, as neurons in both basolateral amygdala (BLA) and gustatory cortex (GC)—anatomically interconnected nodes of the gustatory system—code the emotional valence of taste stimuli (i.e., palatability), in firing rate responses that progress similarly through “epochs.” The fact that palatability-related firing appears one epoch earlier in BLA than GC is broadly consistent with the hypothesis that such information may propagate from the former to the latter. Here, we provide evidence supporting this hypothesis, assaying taste responses in small GC single-neuron ensembles before, during, and after temporarily inactivating BLA in awake rats. BLA inactivation (BLAx) changed responses in 98% of taste-responsive GC neurons, altering the entirety of every taste response in many neurons. Most changes involved reductions in firing rate, but regardless of the direction of change, the effect of BLAx was epoch-specific: while firing rates were changed, the taste specificity of responses remained stable; information about taste palatability, however, which normally resides in the “Late” epoch, was reduced in magnitude across the entire GC sample and outright eliminated in most neurons. Only in the specific minority of neurons for which BLAx enhanced responses did palatability specificity survive undiminished. Our data therefore provide direct evidence that BLA is a necessary component of GC gustatory processing, and that cortical palatability processing in particular is, in part, a function of BLA activity

Suture Materials, 1980s: Properties, Uses, and Abuses

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66057/1/j.1365-4362.1982.tb03154.x.pd

F-theory and Neutrinos: Kaluza-Klein Dilution of Flavor Hierarchy

We study minimal implementations of Majorana and Dirac neutrino scenarios in F-theory GUT models. In both cases the mass scale of the neutrinos m_nu ~ (M_weak)^2/M_UV arises from integrating out Kaluza-Klein modes, where M_UV is close to the GUT scale. The participation of non-holomorphic Kaluza-Klein mode wave functions dilutes the mass hierarchy in comparison to the quark and charged lepton sectors, in agreement with experimentally measured mass splittings. The neutrinos are predicted to exhibit a "normal" mass hierarchy, with masses m_3,m_2,m_1 ~ .05*(1,(alpha_GUT)^(1/2),alpha_GUT) eV. When the interactions of the neutrino and charged lepton sectors geometrically unify, the neutrino mixing matrix exhibits a mild hierarchical structure such that the mixing angles theta_23 and theta_12 are large and comparable, while theta_13 is expected to be smaller and close to the Cabibbo angle: theta_13 ~ theta_C ~ (alpha_GUT)^(1/2) ~ 0.2. This suggests that theta_13 should be near the current experimental upper bound.Comment: v2: 83 pages, 10 figures, references adde

Latent cluster analysis of ALS phenotypes identifies prognostically differing groups

BACKGROUND Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes. METHODS Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method. RESULTS The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001). CONCLUSION The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research

Wall Crossing, Quivers and Crystals

We study the spectrum of BPS D-branes on a Calabi-Yau manifold using the 0+1 dimensional quiver gauge theory that describes the dynamics of the branes at low energies. The results of Kontsevich and Soibelman predict how the degeneracies change. We argue that Seiberg dualities of the quiver gauge theories, which change the basis of BPS states, correspond to crossing the "walls of the second kind." There is a large class of examples, including local del Pezzo surfaces, where the BPS degeneracies of quivers corresponding to one D6 brane bound to arbitrary numbers of D4, D2 and D0 branes are counted by melting crystal configurations. We show that the melting crystals that arise are a discretization of the Calabi-Yau geometry. The shape of the crystal is determined by the Calabi-Yau geometry and the background B-field, and its microscopic structure by the quiver Q. We prove that the BPS degeneracies computed from Q and Q' are related by the Kontsevich Soibelman formula, using a geometric realization of the Seiberg duality in the crystal. We also show that, in the limit of infinite B-field, the combinatorics of crystals arising from the quivers becomes that of the topological vertex. We thus re-derive the Gromov-Witten/Donaldson-Thomas correspondence

‘Fake news’ is the invention of a liar: How false information circulates within the hybrid news system

Alarmed by the oversimplifications related to the ‘fake news’ buzzword, researchers have started to unpack the concept, defining diverse types and forms of misleading news. Most of the existing works in the area consider crucial the intent of the content creator in order to differentiate among different types of problematic information. This article argues for a change of perspective that, by leveraging the conceptual framework of sociocybernetics, shifts from exclusive attention to creators of misleading information to a broader approach that focuses on propagators and, as a result, on the dynamics of the propagation processes. The analytical implications of this perspective are discussed at a micro level (criteria to judge the falsehood of news and to decide to spread it), at a meso level (four possible relations between individual judgements and decisions), and at a macro level (global circulation cascades). The authors apply this theoretical gaze to analyse ‘fake news’ stories that challenge existing models

Evidence for F(uzz) Theory

We show that in the decoupling limit of an F-theory compactification, the internal directions of the seven-branes must wrap a non-commutative four-cycle S. We introduce a general method for obtaining fuzzy geometric spaces via toric geometry, and develop tools for engineering four-dimensional GUT models from this non-commutative setup. We obtain the chiral matter content and Yukawa couplings, and show that the theory has a finite Kaluza-Klein spectrum. The value of 1/alpha_(GUT) is predicted to be equal to the number of fuzzy points on the internal four-cycle S. This relation puts a non-trivial restriction on the space of gauge theories that can arise as a limit of F-theory. By viewing the seven-brane as tiled by D3-branes sitting at the N fuzzy points of the geometry, we argue that this theory admits a holographic dual description in the large N limit. We also entertain the possibility of constructing string models with large fuzzy extra dimensions, but with a high scale for quantum gravity.Comment: v2: 66 pages, 3 figures, references and clarifications adde

Impact of facial conformation on canine health: Brachycephalic Obstructive Airway Syndrome

The domestic dog may be the most morphologically diverse terrestrial mammalian species known to man; pedigree dogs are artificially selected for extreme aesthetics dictated by formal Breed Standards, and breed-related disorders linked to conformation are ubiquitous and diverse. Brachycephaly–foreshortening of the facial skeleton–is a discrete mutation that has been selected for in many popular dog breeds e.g. the Bulldog, Pug, and French Bulldog. A chronic, debilitating respiratory syndrome, whereby soft tissue blocks the airways, predominantly affects dogs with this conformation, and thus is labelled Brachycephalic Obstructive Airway Syndrome (BOAS). Despite the name of the syndrome, scientific evidence quantitatively linking brachycephaly with BOAS is lacking, but it could aid efforts to select for healthier conformations. Here we show, in (1) an exploratory study of 700 dogs of diverse breeds and conformations, and (2) a confirmatory study of 154 brachycephalic dogs, that BOAS risk increases sharply in a non-linear manner as relative muzzle length shortens. BOAS only occurred in dogs whose muzzles comprised less than half their cranial lengths. Thicker neck girths also increased BOAS risk in both populations: a risk factor for human sleep apnoea and not previously realised in dogs; and obesity was found to further increase BOAS risk. This study provides evidence that breeding for brachycephaly leads to an increased risk of BOAS in dogs, with risk increasing as the morphology becomes more exaggerated. As such, dog breeders and buyers should be aware of this risk when selecting dogs, and breeding organisations should actively discourage exaggeration of this high-risk conformation in breed standards and the show ring

CAR-T cell. the long and winding road to solid tumors

Adoptive cell therapy of solid tumors with reprogrammed T cells can be considered the "next generation" of cancer hallmarks. CAR-T cells fail to be as effective as in liquid tumors for the inability to reach and survive in the microenvironment surrounding the neoplastic foci. The intricate net of cross-interactions occurring between tumor components, stromal and immune cells leads to an ineffective anergic status favoring the evasion from the host's defenses. Our goal is hereby to trace the road imposed by solid tumors to CAR-T cells, highlighting pitfalls and strategies to be developed and refined to possibly overcome these hurdles

Field Validity and Feasibility of Four Techniques for the Detection of Trichuris in Simians: A Model for Monitoring Drug Efficacy in Public Health?

Worldwide, millions of people are infected with soil-transmitted helminths, particularly in developing countries. Efforts to control these infections involve periodic mass drug treatment in endemic areas. Since these large-scale interventions are likely to intensify, monitoring of drug efficacy has become a key issue in order to detect the emergence of resistance. At present, the drop in infection intensity is under examination for monitoring the drug efficacy. However, studies comparing detection techniques based on infection intensities are scarce. Moreover, little attention has been addressed to their feasibility and their ability to estimate drug efficacies. We have compared different techniques for the detection of whipworm (Trichuris) in simian stool samples based on prevalence, infection intensities, feasibility and ability to estimate the ‘true’ drug efficacy. We have found that techniques often fail to detect low infection intensities and that not all techniques are appropriate for estimating infection intensities. The time needed to obtain a test result varied from 3.9 to 17.7 min/sample. Finally, accurate estimates of drug efficacy were only obtained in high pre-drug administration infection intensities. To conclude, along with accurate estimates of infection intensities, feasibility is a considerable criterion for the detection techniques used in drug efficacy monitoring programs