Independent evolution of pain insensitivity in African mole-rats: origins and mechanisms

The naked mole-rat (Heterocephalus glaber) is famous for its longevity and unusual physiology. This eusocial species that lives in highly ordered and hierarchical colonies with a single breeding queen, also discovered secrets enabling somewhat pain-free living around 20 million years ago. Unlike most mammals, naked mole-rats do not feel the burn of chili pepper's active ingredient, capsaicin, nor the sting of acid. Indeed, by accumulating mutations in genes encoding proteins that are only now being exploited as targets for new pain therapies (the nerve growth factor receptor TrkA and voltage-gated sodium channel, Na(V)1.7), this species mastered the art of analgesia before humans evolved. Recently, we have identified pain insensitivity as a trait shared by several closely related African mole-rat species. One of these African mole-rats, the Highveld mole-rat (Cryptomys hottentotus pretoriae), is uniquely completely impervious and pain free when confronted with electrophilic compounds that activate the TRPA1 ion channel. The Highveld mole-rat has evolved a biophysical mechanism to shut down the activation of sensory neurons that drive pain. In this review, we will show how mole-rats have evolved pain insensitivity as well as discussing what the proximate factors may have been that led to the evolution of pain-free traits

Ferroelectricity Induced by Acentric Spin-Density Waves in YMn2O5

The commensurate and incommensurate magnetic structures of the magnetoelectric system YMn2O5, as determined from neutron diffraction, were found to be spin-density waves lacking a global center of symmetry. We propose a model, based on a simple magnetoelastic coupling to the lattice, which enables us to predict the polarization based entirely on the observed magnetic structure. Our data accurately reproduce the temperature dependence of the spontaneous polarization, particularly its sign reversal at the commensurate-incommensurate transition

Specific paucity of unmyelinated C-fibers in cutaneous peripheral nerves of the African naked-mole rat: comparative analysis using six species of bathyergidae

In mammalian peripheral nerves, unmyelinated C-fibers usually outnumber myelinated A-fibers. Using transmission electron microscopy we recently showed that the saphenous nerve of the naked mole-rat (Heterocephalus glaber) has a C-fiber deficit manifested as a substantially lower C:A-fiber ratio compared to other mammals. Here we determined the uniqueness of this C-fiber deficit by performing a quantitative anatomical analysis of several peripheral nerves in five further members of the Bathyergidae mole-rat family: silvery (Heliophobius argenteocinereus), giant (Fukomys mechowii), Damaraland (Fukomys damarensis), Mashona (Fukomys darlingi) and Natal (Cryptomys hottentotus natalensis) mole-rats. In the largely cutaneous saphenous and sural nerves we found that the naked mole-rat had the lowest C:A-fiber ratio (~1.5:1 compared to ~3:1), whereas in nerves innervating both skin and muscle (common peroneal and tibial) or just muscle (lateral/medial gastrocnemius), this pattern was mostly absent. We asked whether lack of hair follicles alone accounts for the C-fiber paucity using a mouse model, which loses virtually all its hair as a consequence of conditional deletion of the beta-catenin gene in the skin. These beta-catenin loss-of function mice (beta-cat LOF mice) displayed only a mild decrease in C:A-fiber ratio compared to wild-type mice (4.42 compared to 3.81). We suggest that the selective cutaneous C-fiber deficit in the cutaneous nerves of naked mole-rats is unlikely to be primarily due to lack of skin hair follicles. Possible mechanisms contributing to this unique peripheral nerve anatomy are discussed

Weak gravity in DGP braneworld model

We analyze the weak gravity in the braneworld model proposed by Dvali-Gabadadze-Porrati, in which the unperturbed background spacetime is given by five dimensional Minkowski bulk with a brane which has the induced Einstein Hilbert term. This model has a critical length scale $r_c$. Naively, we expect that the four dimensional general relativity (4D GR) is approximately recovered at the scale below $r_c$. However, the simple linear perturbation does not work in this regime. Only recently the mechanism to recover 4D GR was clarified under the restriction to spherically symmetric configurations, and the leading correction to 4D GR was derived. Here, we develop an alternative formulation which can handle more general perturbations. We also generalize the model by adding bulk cosmological constant and the brane tension.Comment: 7 pages, 1 figure, references adde

In Vitro Evaluation of an Active Heat-and-Moisture Exchanger: The Hygrovent Gold

BACKGROUND: To improve the heat and humidification that can be achieved with aheat-and-moisture exchanger (HME),a hybrid active (ie,adds heat and water) HME,the Hygrovent Gold,was developed. We evaluated in vitro the performance of theHygrovent Gold. METHODS: We tested the Hygrovent Gold (with and without its supplemental heat andmoisture options activated),the Hygrobac,and the Hygrovent S. We measured theabsolute humidity,using a test lung ventilated at minute volumes of 5,10,and15 L/min,in normothermic (expired temperature 34 degrees C) and hypothermic(expired temperature 28 degrees C) conditions. We also measured the HMEs' flowresistance and weight after 24 h and 48 h. RESULTS: In its active mode the Hygrovent Gold provided the highest absolutehumidity,independent of minute volume,in both normothermia and hypothermia. Therespective normothermia and hypothermia absolute humidity values at 10 L/min were36.3 + 1.3 mg/L and 27.1 + 1.0 mg/L with the active Hygrovent Gold,33.9 + 0.5mg/L and 24.2 + 0.8 mg/L with the passive Hygrovent Gold,33.8 + 0.56 mg/L and24.4 + 0.4 mg/L with the Hygrobac,and 33.9 + 0.8 mg/L and 24.6 + 0.6 mg/L withthe Hygrovent S. The efficiency of the tested HMEs did not change over time. At24 h and 48 h the increase in weight and flow resistance was highest in theactive Hygrovent Gold. CONCLUSIONS: The passive Hygrovent Gold provided adequate heat and moisture innormothermia,but the active Hygrovent Gold provided the highest humidity,inboth normothermia and hypothermia

Exotic smooth structures and symplectic forms on closed manifolds

We give a short proof of the (known) result that there are no Kaehler structures on exotic tori. This yields a negative solution to a problem posed by Benson and Gordon. W discuss the symplectic version of the problem and analyze results which yield an evidence for the conjecture that there are no symplectic structures on exotic tori.Comment: AMSLaTeX, 16 pages, a new version. A survey of the symplectic version of the problem is adde

New agegraphic dark energy in Horava-Lifshitz cosmology

We investigate the new agegraphic dark energy scenario in a universe governed by Horava-Lifshitz gravity. We consider both the detailed and non-detailed balanced version of the theory, we impose an arbitrary curvature, and we allow for an interaction between the matter and dark energy sectors. Extracting the differential equation for the evolution of the dark energy density parameter and performing an expansion of the dark energy equation-of-state parameter, we calculate its present and its low-redshift value as functions of the dark energy and curvature density parameters at present, of the Horava-Lifshitz running parameter $\lambda$, of the new agegraphic dark energy parameter $n$, and of the interaction coupling $b$. We find that $w_0=-0.82^{+0.08}_{-0.08}$ and $w_1=0.08^{+0.09}_{-0.07}$. Although this analysis indicates that the scenario can be compatible with observations, it does not enlighten the discussion about the possible conceptual and theoretical problems of Horava-Lifshitz gravity.Comment: 17 pages, no figures, version published at JCA