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71.
Kristof Veitschegger Christian Kolb Eli Amson Marcelo R. Sánchez-Villagra 《Historical Biology》2019,31(4):510-516
AbstractLongevity and other life history variables are key to understanding evolutionary processes and the biology of extinct animals. For the past 20 years, the lifespan of cave bears received an increased interest. Studies focusing on incremental lines of tooth cementum resulted in detailed mortality patterns from different localities. In this review, we summarise literature on age estimation as well as mortality of different European cave bear localities and present novel data on longevity from 94 teeth originating from 20 European localities. Additionally, the relative tooth emergence pattern of the permanent dentition is investigated under the Schultz’s rule framework of possible life history implications. For this, the known sequences of extant bear species are compared with the one of cave bears. Our results suggest that the typical duration of the life of cave bears was 19 years but data from literature show that in rare cases ages of up to 30–32 years were achieved. Additionally, we present the oldest known age for the Middle Pleistocene cave bear Ursus deningeri, 29 years. The tooth eruption pattern of cave bears exhibits a heterochronic shift that implies, under the assumption of Schulz’ rule, a slightly faster life history than closely related species. 相似文献
72.
Signaling by bone morphogenetic proteins (BMPs) plays pivotal roles in embryogenesis, adult tissue homeostasis, and disease. Recent studies revealed that the well-established WNT agonist R-spondin 2 (RSPO2) is also a BMP receptor (BMP receptor type 1A) antagonist, with roles in early Xenopus embryogenesis and human acute myeloid leukemia (AML). To uncouple the BMP antagonist function from the WNT agonist function and to promote development of AML therapeutics, here we identified a 10-mer peptide (RW) derived from the thrombospondin 1 domain of RSPO2, which specifically prevents binding between RSPO2 and BMP receptor type 1A without altering WNT signaling. We also show that a corresponding RW dendrimer (RWd) exhibiting improved half-life relieves inhibition of BMP receptor signaling by RSPO2 in human AML cells, reduces cell growth, and induces differentiation. Moreover, microinjection of RWd in Xenopus embryos ventralizes the dorsoventral embryonic patterning by upregulating BMP signaling without affecting WNT signaling. Our study corroborates the function of RSPO2 as a BMP receptor antagonist and provides a proof of concept for pharmacologically uncoupling BMP antagonist from WNT agonist functions of RSPO2 using the inhibitor peptide RWd with enhanced target selectivity and limited side effects. 相似文献
73.
David C. Lees Rodolphe Rougerie Christof
Zeller‐Lukashort Niels P. Kristensen 《Zoologica scripta》2010,39(6):642-661
Lees, D. C., Rougerie, R., Zeller‐Lukashort, C. & Kristensen, N. P. (2010). DNA mini‐barcodes in taxonomic assignment: a morphologically unique new homoneurous moth clade from the Indian Himalayas described in Micropterix (Lepidoptera, Micropterigidae). —Zoologica Scripta, 39, 642–661. The first micropterigid moths recorded from the Himalayas, Micropterix cornuella sp. n. and Micropterix longicornuella sp. n. (collected, respectively, in 1935 in the Arunachel Pradesh Province and in 1874 in Darjeeling, both Northeastern India) constitute a new clade, which is unique within the family because of striking specializations of the female postabdomen: tergum VIII ventral plate forming a continuous sclerotized ring, segment IX bearing a pair of strongly sclerotized lateroventral plates, each with a prominent horn‐like posterior process. Fore wing vein R unforked, all Rs veins preapical; hind wing devoid of a discrete vein R. The combination of the two first‐mentioned vein characters suggests close affinity to the large Palearctic genus Micropterix (to some species of which the members of the new clade bear strong superficial resemblance). Whilst absence of the hind wing R is unknown in that genus, this specialization is not incompatible with the new clade being subordinate within it. A 136‐bp fragment of Cytochrome oxidase I successfully amplified from both of the 75‐year‐old specimens strongly supports this generic assignment. Translated to amino acids, this DNA fragment is highly diagnostic of this genus, being identical to that of most (16 of the 26) Micropterix species studied comparatively here, 1–4 codons different from nine other species (including Micropterix wockei that in phylogenetic analyses we infer to be sister to other examined species), whilst 7–15 codons different to other amphiesmenopteran genera examined here. A dating analysis also suggests that the large clade excluding M. wockei to which M. cornuella belongs appeared <31 million years ago. These findings encourage discovery of a significant radiation of Micropterix in the Himalayan region. Our analysis has more general implications for testing the assignment of DNA mini‐barcodes to a taxon, in cases such as museum specimens where the full DNA barcode cannot be recovered. 相似文献
74.
Virus-neutralizing monoclonal antibody expressed in milk of transgenic mice provides full protection against virus-induced encephalitis 总被引:4,自引:0,他引:4
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Neutralizing antibodies represent a major host defense mechanism against viral infections. In mammals, passive immunity is provided by neutralizing antibodies passed to the offspring via the placenta or the milk as immunoglobulin G and secreted immunoglobulin A. With the long-term goal of producing virus-resistant livestock, we have generated mice carrying transgenes that encode the light and heavy chains of an antibody that is able to neutralize the neurotropic JHM strain of murine hepatitis virus (MHV-JHM). MHV-JHM causes acute encephalitis and acute and chronic demyelination in susceptible strains of mice and rats. Transgene expression was targeted to the lactating mammary gland by using the ovine beta-lactoglobulin promoter. Milk from these transgenic mice contained up to 0.7 mg of recombinant antibody/ml. In vitro analysis of milk derived from different transgenic lines revealed a linear correlation between antibody expression and virus-neutralizing activity, indicating that the recombinant antibody is the major determinant of MHV-JHM neutralization in murine milk. Offspring of transgenic and control mice were challenged with a lethal dose of MHV-JHM. Litters suckling nontransgenic dams succumbed to fatal encephalitis, whereas litters suckling transgenic dams were fully protected against challenge, irrespective of whether they were transgenic. This demonstrates that a single neutralizing antibody expressed in the milk of transgenic mice is sufficient to completely protect suckling offspring against MHV-JHM-induced encephalitis. 相似文献
75.
Mice lacking the poly(ADP-ribose) polymerase gene are resistant to pancreatic beta-cell destruction and diabetes development induced by streptozocin 总被引:15,自引:0,他引:15
Burkart V Wang ZQ Radons J Heller B Herceg Z Stingl L Wagner EF Kolb H 《Nature medicine》1999,5(3):314-319
Human type 1 diabetes results from the selective destruction of insulin-producing pancreatic beta cells during islet inflammation. Cytokines and reactive radicals released during this process contribute to beta-cell death. Here we show that mice with a disrupted gene coding for poly (ADP-ribose) polymerase (PARP-/- mice) are completely resistant to the development of diabetes induced by the beta-cell toxin streptozocin. The mice remained normoglycemic and maintained normal levels of total pancreatic insulin content and normal islet ultrastructure. Cultivated PARP-/- islet cells resisted streptozocin-induced lysis and maintained intracellular NAD+ levels. Our results identify NAD+ depletion caused by PARP activation as the dominant metabolic event in islet-cell destruction, and provide information for the development of strategies to prevent the progression or manifestation of the disease in individuals at risk of developing type 1 diabetes. 相似文献
76.
77.
Haffner C Frauli M Topp S Irmler M Hofmann K Regula JT Bally-Cuif L Haass C 《The EMBO journal》2004,23(15):3041-3050
Nodals are signaling factors of the transforming growth factor-beta (TGFbeta) superfamily with a key role in vertebrate development. They control a variety of cell fate decisions required for the establishment of the embryonic body plan. We have identified two highly conserved transmembrane proteins, Nicalin and Nomo (Nodal modulator, previously known as pM5), as novel antagonists of Nodal signaling. Nicalin is distantly related to Nicastrin, a component of the Alzheimer's disease-associated gamma-secretase, and forms a complex with Nomo. Ectopic expression of both proteins in zebrafish embryos causes cyclopia, a phenotype that can arise from a defect in mesendoderm patterning mediated by the Nodal signaling pathway. Accordingly, downregulation of Nomo resulted in an increase in anterior axial mesendoderm and the development of an enlarged hatching gland. Inhibition of Nodal signaling by ectopic expression of Lefty was rescued by reducing Nomo levels. Furthermore, Nodal- as well as Activin-induced signaling was inhibited by Nicalin and Nomo in a cell-based reporter assay. Our data demonstrate that the Nicalin/Nomo complex antagonizes Nodal signaling during mesendodermal patterning in zebrafish. 相似文献
78.
Lang PA Kaiser S Myssina S Birka C Weinstock C Northoff H Wieder T Lang F Huber SM 《Cellular microbiology》2004,6(4):391-400
Haemolysin Kanagawa, a toxin from Vibrio parahaemolyticus, is known to trigger haemolysis. Flux studies indicated that haemolysin forms a cation channel. In the present study, channel properties were elucidated by patch clamp and functional significance of ion fluxes by fluorescence-activated cell sorting (FACS) analysis. Treatment of human erythrocytes with 1 U ml-1 haemolysin within minutes induces a non-selective cation permeability. Moreover, haemolysin activates clotrimazole-sensitive K+ channels, pointing to stimulation of Ca2+-sensitive Gardos channels. Haemolysin (1 U ml-1) leads within 5 min to slight cell shrinkage, which is reversed in Ca2+-free saline. Erythrocytes treated with haemolysin (0.1 U ml-1) do not undergo significant haemolysis within the first 60 min. Replacement of extracellular Na+ with NMDG+ leads to slight cell shrinkage, which is potentiated by 0.1 U ml-1 haemolysin. According to annexin binding, treatment of erythrocytes with 0.1 U ml-1 haemolysin leads within 30 min to breakdown of phosphatidylserine asymmetry of the cell membrane, a typical feature of erythrocyte apoptosis. The annexin binding is significantly blunted at increased extracellular K+ concentrations and by K+ channel blocker clotrimazole. In conclusion, haemolysin Kanagawa induces cation permeability and activates endogenous Gardos K+ channels. Consequences include breakdown of phosphatidylserine asymmetry, which depends at least partially on cellular loss of K+. 相似文献
79.
R-Spondin2 is a secreted activator of Wnt/beta-catenin signaling and is required for Xenopus myogenesis 总被引:4,自引:0,他引:4
Kazanskaya O Glinka A del Barco Barrantes I Stannek P Niehrs C Wu W 《Developmental cell》2004,7(4):525-534
We have carried out a small pool expression screen for modulators of the Wnt/beta-catenin pathway and identified Xenopus R-spondin2 (Rspo2) as a secreted activator of this cascade. Rspo2 is coexpressed with and positively regulated by Wnt signals and synergizes with Wnts to activate beta-catenin. Analyses of functional interaction with components of the Wnt/beta-catenin pathway suggest that Rspo2 functions extracellularly at the level of receptor ligand interaction. In addition to activating the Wnt/beta-catenin pathway, Rspo2 overexpression blocks Activin, Nodal, and BMP4 signaling in Xenopus, raising the possibility that it may negatively regulate the TGF-beta pathway. Antisense Morpholino experiments in Xenopus embryos and RNAi experiments in HeLa cells reveal that Rspo2 is required for Wnt/beta-catenin signaling. In Xenopus embryos depleted of Rspo2, the muscle markers myoD and myf5 fail to be activated and later muscle development is impaired. Thus, Rspo2 functions in a positive feedback loop to stimulate the Wnt/beta-catenin cascade. 相似文献
80.
Only a few mitochondrial proteins are encoded by the organellar genome. The majority of mitochondrial proteins are nuclear encoded and thus have to be transported into the organelle from the cytosol. Within the mitochondrion proteins have to be sorted into one of the four sub-compartments: the outer or inner membranes, the intermembrane space or the matrix. These processes are mediated by complex protein machineries within the different compartments that act alone or in concert with each other. The translocation machinery of the outer membrane is formed by a multi-subunit protein complex (TOM complex), that is built up by signal receptors and the general import pore (GIP). The inner membrane houses two multi-subunit protein complexes that each handles special subsets of mitochondrial proteins on their way to their final destination. According to their primary function these two complexes have been termed the pre-sequence translocase (or TIM23 complex) and the protein insertion complex (or TIM22 complex). The identification of components of these complexes and the analysis of the molecular mechanisms underlying their function are currently an exciting and fast developing field of molecular cell biology. 相似文献