Origination of antlerogenesis

Antlers are unique appendages. They are shed and rebuilt at intervals, and are synapomorphic for all living Cervidae (except for the Chinese water deer, Hydropotes inermis , in which they have presumably been lost). The antlerogenic process is controlled by a complex interaction of fluctuating levels of several hormones, most importantly testosterone. The oldest antler remains are recorded from the early Miocene; these have been interpreted as non‐deciduous appendages because of supposed permanent skin coverage and the lack of a burr (a well‐developed osseous protuberance around the base of the antler, which is always present in extant cervids). The aim of this study is to test the hypothesis that antler shedding was possible in these early Miocene cervids. Antlers of all extant and eight Miocene cervid genera, including burr‐less antler fragments of the earliest cervids Procervulus , Ligeromeryx , and Lagomeryx were studied. An extensive comparative morphological analysis of external features of the antler, and of the abscission area and the base of the antler in particular, was undertaken. The results indicate that a regular, porous, and rugose abscission surface at the proximal end of the antler indicates antler shedding in both living and fossil cervids. The antler shedding mechanism must therefore have already been present in all early/mid Miocene cervid genera included in this study. On this basis, it is suggested that the presence of a burr is not prerequisite in order to shed antlers, that the presence of perpetual antlers has not yet been verified, and that the process of shedding and regeneration developed with the first appearance of these organs. This insight is particularly important for the systematic classification of early Miocene species as Cervidae, because the absence of the antler shedding and rebuilding mechanism would exclude them from the taxon Cervidae and from any relationship with extant cervids. J. Morphol. 278:182–202, 2017. © 2016 Wiley Periodicals,Inc.     

Ultrastructural contributions to an understanding of the cellular mechanisms involved in lizard skin shedding with comments on the function and evolution of a unique Lepidosaurian phenomenon

Previous reports on the fine structure of lizard epidermis are confirmed and extended by SEM and TEM observations of cell differentiation and the form of shed material from the American anole Anolis carolinensis. Attention is drawn to two issues: 1) the tips of the spinules arising from the mature oberhautchen are markedly curved; this morphology can be seen during differentiation; 2) the median keels of scales from all parts of the body show “naked” oberhautchen cells that lack characteristic spinules, but have a membrane morphology comprising a complex system of serpentine microridges. Maderson's ([1966] J. Morphol. 119:39–50) “zip-fastener” model for the role of the shedding complex formed by the clear layer and oberhautchen is reviewed and extended in the light of recent SEM data. Apparently periodic lepidosaurian sloughing permits somatic growth; understanding how the phenomenon is brought about requires integration of data from the organismic to the molecular level. The diverse forms of integumentary microornamentation (MO) reported in the literature can be understood by considering how the cellular events occurring during the renewal phase prior to shedding relate to the emergence of the form-function complex of the β-layer, which provides physical protection. Issues concerning the evolutionary origin of lepidosaurian skin-shedding are discussed. J. Morphol. 236:1–24, 1998. © 1998 Wiley-Liss, Inc.     

The shedding of syndecan-4 and syndecan-1 from HeLa cells and human primary macrophages is accelerated by SDF-1/CXCL12 and mediated by the matrix metalloproteinase-9

We recently demonstrated that stromal cell-derived factor-1(SDF-1/CXCL12) forms complexes with CXCR4, but also with syndecan-4expressed by human primary lymphocytes and macrophages, andHeLa cells. We also suggested that syndecan-4 behaves as a SDF-1-signalingmolecule. Here, we demonstrate that SDF-1 strongly acceleratesthe shedding of syndecan-4 ectodomains and to a lesser extentthat of syndecan-1 from HeLa cells. The fact that this accelerationwas not inhibited by the CXCR4 antagonist AMD3100, anti-CXCR4mAb 12G5, and CXCR4 gene silencing suggests its CXCR4-independence.Pre-treating the cells with heparitinases I, III, or with theprotein kinase C (PKC) inhibitor, bisindolylmaleimide, significantlyinhibited this accelerated shedding, which suggests the involvementof both cell-surface heparan sulfate and PKC transduction pathway.In contrast, Map Kinase or NF-B pathway inhibitors had no effect.Moreover, SDF-1 increases the matrix metalloproteinase-9 (MMP-9)mRNA level as well as MMP-9 activity in HeLa cells, and MMP-9silencing by RNA interference strongly decreases the syndecan-1and -4 ectodomain shedding accelerated by SDF-1. Finally, SDF-1also accelerates in a CXCR4-independent manner, the sheddingof syndecan-1 and -4 from human primary macrophages, which issignificantly inhibited by anti-MMP-9 antibodies. This stronglyindicates the role of MMP-9 in these events occurring in botha tumoral cell line and in human primary macrophages. BecauseMMP-9 plays a crucial role in extracellular matrix degradationduring cancer cell metastasis and invasion, and shed ectodomainsof syndecans may likely be involved in tumor cell proliferation,these data further indicate the multiplicity of the roles playedby SDF-1 on tumor cell biology.     

Porcine circovirus type 2 (PCV2) vaccination is effective in reducing disease and PCV2 shedding in semen of boars concurrently infected with PCV2 and Mycoplasma hyopneumoniae

The objectives were to determine whether the amount of porcine circovirus type 2 (PCV2) shed in semen increased in boars experimentally coinfected with Mycoplasma hyopneumoniae (MHYO), and whether PCV2 vaccination of boars prior to PCV2 exposure reduced PCV2 viremia and virus shedding in semen. Twelve specific-pathogen-free PCV2- and MHYO-naïve boars were randomly and equally assigned to one of four groups. Six boars were vaccinated against PCV2 (VAC) on Day 0; three PCV2 vaccinated and three non-vaccinated boars were inoculated with MHYO on Day 21, and all boars were challenged with PCV2 on Day 35. The four treatment groups included PCV2-Infected (I), VAC-PCV2-I, MHYO-PCV2-Coinfected (CoI), and VAC-MHYO-PCV2-CoI. Semen, blood swabs, feces, and serum samples were collected weekly until Day 70. All vaccinated boars had seroconverted to PCV2 by Day 35. Between Days 28 and 35, MHYO boars developed moderate respiratory disease, characterized by coughing, respiratory distress, mucopurulent nasal discharge and loss of body condition. One MHYO-PCV2-CoI boar died on Day 50. Boars in the PCV2-I and MHYO-PCV2-CoI groups had significantly higher PCV2 DNA loads in blood swabs than the remaining boars. Moreover, PCV2 vaccination significantly reduced the incidence and amount of PCV2 shedding in semen and feces. In summary, although concurrent MHYO infection did not influence PCV2 shedding patterns, coinfection of boars with PCV2 and MHYO resulted in severe clinical disease and viral shedding was significantly decreased by PCV2 vaccination.     

Dopamine-dependent ectodomain shedding and release of epidermal growth factor in developing striatum: target-derived neurotrophic signaling (Part 2)

Epidermal growth factor (EGF) and structurally related peptides promote neuronal survival and the development of midbrain dopaminergic neurons; however, the regulation of their production has not been fully elucidated. In this study, we found that the treatment of striatal cells with dopamine agonists enhances EGF release both in vivo and in vitro. We prepared neuron-enriched and non-neuronal cell-enriched cultures from the striatum of rat embryos and challenged those with various neurotransmitters or dopamine receptor agonists. Dopamine and a dopamine D(1) -like receptor agonist (SKF38393) triggered EGF release from neuron-enriched cultures in a dose-dependent manner. A D(2) -like agonist (quinpirole) increased EGF release only from non-neuronal cell-enriched cultures. The EGF release from striatal neurons and non-neuronal cells was concomitant with ErbB1 phosphorylation and/or with the activation of a disintegrin and metalloproteinase and matrix metalloproteinase. The EGF release from neurons was attenuated by an a disintegrin and metalloproteinase/matrix metalloproteinase inhibitor, GM6001, and a calcium ion chelator, BAPTA/AM. Transfection of cultured striatal neurons with alkaline phosphatase-tagged EGF precursor cDNA confirmed that dopamine D(1) -like receptor stimulation promoted both ectodomain shedding of the precursor and EGF release. Therefore, the activation of striatal dopamine receptors induces shedding and release of EGF to provide a retrograde neurotrophic signal to midbrain dopaminergic neurons.     

Into turbulent air: size-dependent effects of von Kármán vortex streets on hummingbird flight kinematics and energetics

Animal fliers frequently move through a variety of perturbed flows during their daily aerial routines. However, the extent to which these perturbations influence flight control and energetic expenditure is essentially unknown. Here, we evaluate the kinematic and metabolic consequences of flight within variably sized vortex shedding flows using five Anna''s hummingbirds feeding from an artificial flower in steady control flow and within vortex wakes produced behind vertical cylinders. Tests were conducted at three horizontal airspeeds (3, 6 and 9 m s⁻¹) and using three different wake-generating cylinders (with diameters equal to 38, 77 and 173% of birds'' wing length). Only minimal effects on wing and body kinematics were demonstrated for flight behind the smallest cylinder, whereas flight behind the medium-sized cylinder resulted in significant increases in the variances of wingbeat frequency, and variances of body orientation, especially at higher airspeeds. Metabolic rate was, however, unchanged relative to that of unperturbed flight. Hummingbirds flying within the vortex street behind the largest cylinder exhibited highest increases in variances of wingbeat frequency, and of body roll, pitch and yaw amplitudes at all measured airspeeds. Impressively, metabolic rate under this last condition increased by up to 25% compared with control flights. Cylinder wakes sufficiently large to interact with both wings can thus strongly affect stability in flight, eliciting compensatory kinematic changes with a consequent increase in flight metabolic costs. Our findings suggest that vortical flows frequently encountered by aerial taxa in diverse environments may impose substantial energetic costs.     

MICA 脱落与肿瘤免疫逃逸：肿瘤免疫治疗新靶标和新策略

MHC Ⅰ类链相关分子（MICA）是自然杀伤细胞和T 细胞上NKG2D 受体的主要活化性配体,在上皮源性肿瘤细胞表面过表达。NKG2D 与MICA 的结合可有效刺激效应细胞对肿瘤细胞的细胞毒作用。然而,临床观察表明,MICA 会在肿瘤的增殖过程中脱落而形成可溶性MICA（sMICA）,这被认为是肿瘤细胞逃脱NKG2D 介导的免疫监视的重要原因。综述在肿瘤细胞中MICA 和NKG2D 的表达与功能、sMICA 的形成与肿瘤免疫逃逸的关联以及介导MICA 脱落的机制,由此探讨肿瘤免疫治疗的新靶点和新策略。     

EphrinA/EphA‐induced ectodomain shedding of neural cell adhesion molecule regulates growth cone repulsion through ADAM10 metalloprotease

EphrinA/EphA‐dependent axon repulsion is crucial for synaptic targeting in developing neurons but downstream molecular mechanisms remain obscure. Here, it is shown that ephrinA5/EphA3 triggers proteolysis of the neural cell adhesion molecule (NCAM) by the metalloprotease a disintegrin and metalloprotease (ADAM)10 to promote growth cone collapse in neurons from mouse neocortex. EphrinA5 induced ADAM10 activity to promote ectodomain shedding of polysialic acid‐NCAM in cortical neuron cultures, releasing a ~ 250 kDa soluble fragment consisting of most of its extracellular region. NCAM shedding was dependent on ADAM10 and EphA3 kinase activity as shown in HEK293T cells transfected with dominant negative ADAM10 and kinase‐inactive EphA3 (K653R) mutants. Purified ADAM10 cleaved NCAM at a sequence within the E‐F loop of the second fibronectin type III domain (Leu⁶⁷¹‐Lys⁶⁷²/Ser⁶⁷³‐Leu⁶⁷⁴) identified by mass spectrometry. Mutations of NCAM within the ADAM10 cleavage sequence prevented EphA3‐induced shedding of NCAM in HEK293T cells. EphrinA5‐induced growth cone collapse was dependent on ADAM10 activity, was inhibited in cortical cultures from NCAM null mice, and was rescued by WT but not ADAM10 cleavage site mutants of NCAM. Regulated proteolysis of NCAM through the ephrin5/EphA3/ADAM10 mechanism likely impacts synapse development, and may lead to excess NCAM shedding when disrupted, as implicated in neurodevelopmental disorders such as schizophrenia.

     

Inhibitory effects of oroxylin A on endothelial protein C receptor shedding in vitro and in vivo

Endothelial cell protein C receptor (EPCR) plays important roles in blood coagulation and inflammation. EPCR activity is markedly changed by ectodomain cleavage and release as the soluble EPCR. EPCR can be shed from the cell surface, which is mediated by tumor necrosis factor-α converting enzyme (TACE). Oroxylin A (OroA), a major component of Scutellaria baicalensis Georgi, is known to exhibit anti-angiogenic, antiinflammation, and anti-invasive activities. However, little is known about the effects of OroA on EPCR shedding. Data showed that OroA induced potent inhibition of phorbol-12-myristate 13-acetate (PMA), tumor necrosis factor (TNF)-α, interleukin (IL)-1β and on cecal ligation and puncture (CLP)-induced EPCR shedding through suppression of TACE expression and activity. In addition, treatment with OroA resulted in reduced PMA-stimulated phosphorylation of p38, extracellular regulated kinases (ERK) 1/2, and c-Jun N-terminal kinase (JNK). These results demonstrate the potential of OroA as an anti-sEPCR shedding reagent against PMA and CLP-mediated EPCR shedding. [BMB Reports 2014; 47(6): 336-341]