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The Mind's Eye is a Big Finish Productions audio drama based on the long-running British science fiction television series Doctor Who. It is a three-part story written by Colin Brake and was released alongside a one-part story, Mission of the Viyrans.

Plot
The Doctor, Erimem and Peri have gone their separate ways. The Doctor is wandering on a nameless paradise planet filled with murderous primates (but only at night) and carnivorous plants. Erimem is the Queen of a space colony empire, New Cairo, and is suffering a rebellion, while Peri's stepson and new husband are causing problems to her domestic bliss.

Cast
The Doctor — Peter Davison
Peri — Nicola Bryant
Erimem — Caroline Morris
Hayton — Owen Teale
Major Takol — Rebecca Front
Kyle — Thomas Brodie-Sangster
Ukarme — Richard Laing
Andree — Nicola Weeks

Behind-the-scenes
This story leads directly into the audio drama The Bride of Peladon.

The hallucinogenic plants in this story reappear in Brotherhood of the Daleks.

Mission of the Viyrans
Mission of the Viyrans is a Big Finish Productions audio drama based on the long-running British science fiction television series Doctor Who. It is a one-part story written by Nicholas Briggs and was released alongside a three-part story, The Mind's Eye.

The Doctor and Peri encounter the time travelling Viyrans on a holiday planet.

Cast
The Doctor — Peter Davison
Peri — Nicola Bryant
 Lawrence – Peter Sowerbutts
 Chris – Philip Childs

Behind-the-scenes
Mission of the Viyrans completes the "Virus Strand" story arc, which also includes the audio dramas Urgent Calls, Urban Myths and The Vanity Box.

This story marks the first appearance of the Viyrans for Big Finish.  They first appeared in the short story "No One Died", also written by Nicholas Briggs, featuring the Tenth Doctor and published in the 2007 Doctor Who Storybook.  The Viyrans return against the Sixth Doctor in Patient Zero.

External links
Big Finish Productions – The Mind's Eye

2007 audio plays
Fifth Doctor audio plays


PHILADELPHIA -- The Eagles embraced the underdog role.
Boy, did they embrace it.
So much so that a pair of veterans, right tackle Lane Johnson and defensive end Chris Long, went out and bought dog masks -- German shepherd masks, to be precise -- to sport in order to get into full character in the days leading up to the game.
"Me and Chris Long were talking [at lunch], and everybody's calling us underdogs, so hey, let's go get us a dog mask," Johnson said. "That's what we did."
The sixth-seeded Atlanta Falcons entered Saturday's divisional-round game in Philadelphia as three-point favorites. It was the first time in NFL history that a top seed was not favored in its first postseason game.
The Eagles organization pounced on this angle, playing up the idea that they were being disrespected. The Eagles even hung up copies of analyst predictions to show how many people were siding with the Falcons.
Philly used that edge to help fight past Atlanta 15-10 and into the NFC Championship Game.
And the dog masks were donned after the game.
"When did Carson [Wentz] go down? Since that point, no one's given us a chance," Eagles coach Doug Pederson coach, referring to the QB's Dec. 10 ACL tear. "I understand Carson's a great player, but every week our guys are hearing the same thing. Now, all of a sudden, we're not good enough? We're 13-3, best record in football, home-field advantage throughout.
The loss of Wentz certainly factored into the questions about the Eagles' playoff viability, as did the shaky play of his replacement, Nick Foles, to close out the regular season. On Saturday, the offense was up and down against Atlanta and found the end zone just once, but it was backed by a lights-out defense that came up with a big stand in the shadow of the end zone to close the game.
The Eagles advance as a result and await the winner of Sunday's game between the New Orleans Saints and Minnesota Vikings. Philadelphia will have home-field advantage again, but as of Saturday, would be underdogs against either foe (Vikings -4.5, Saints -3), per the Westgate Sportsbook.
The Eagles certainly earned some respect by taking care of the Falcons, but Johnson is holding onto the dog mask, just in case.


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Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex
Kazuhiko Namekata, Chikako Harada, Choji Taya, Xiaoli Guo, Hideo Kimura, Luis F. Parada, and Takayuki Harada
aDepartment of Molecular Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo 183-8526, Japan;
bDepartment of Developmental Biology and Kent Waldrep Foundation Center for Basic Research on Nerve Growth and Regeneration, University of Texas Southwestern Medical Center, Dallas, TX 75390;
cDepartment of Laboratory Animal Science, Tokyo Metropolitan Institute of Medical Science, Setagaya, Tokyo 156-8506, Japan; and
dDepartment of Molecular Genetics, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo 187-8502, Japan
PNAS April 20, 2010 107 (16) 7586-7591; https://doi.org/10.1073/pnas.0914514107
Kazuhiko Namekata
Chikako Harada
Choji Taya
Xiaoli Guo
Hideo Kimura
Luis F. Parada
Takayuki Harada
Edited by Thomas C. Südhof, Stanford University School of Medicine, Palo Alto, CA, and approved March 16, 2010 (received for review December 18, 2009)
Atypical Rho-guanine nucleotide exchange factors (Rho-GEFs) that contain Dock homology regions (DHR-1 and DHR-2) are expressed in a variety of tissues; however, their functions and mechanisms of action remain unclear. We identify key conserved amino acids in the DHR-2 domain that are critical for the catalytic activity of Dock-GEFs (Dock1–4). We further demonstrate that Dock-GEFs directly associate with WASP family verprolin-homologous (WAVE) proteins through the DHR-1 domain. Brain-derived neurotrophic factor (BDNF)-TrkB signaling recruits the Dock3/WAVE1 complex to the plasma membrane, whereupon Dock3 activates Rac and dissociates from the WAVE complex in a phosphorylation-dependent manner. BDNF induces axonal sprouting through Dock-dependent Rac activation, and adult transgenic mice overexpressing Dock3 exhibit enhanced optic nerve regeneration after injury without affecting WAVE expression levels. Our results highlight a unique mechanism through which Dock-GEFs achieve spatial and temporal restriction of WAVE signaling, and identify Dock-GEF activity as a potential therapeutic target for axonal regeneration.
Dock family proteins
brain-derived neurotrophic factor
axonal regeneration
The Rho-family GTPases (Rho-GTPases, including Rac1, Cdc42, and RhoA), which are best known for their roles in regulating the actin cytoskeleton, have been implicated in a broad spectrum of biological functions, such as cell motility and invasion, cell growth, cell survival, cell polarity, clearance of apoptotic cells, membrane protrusion, and axonal guidance (1, 2). Activation signals from Rac1 and Cdc42 are relayed to the actin-nucleating complex Arp2/3 by a family of proteins that includes Wiskott–Aldrich syndrome protein (WASP) and WASP family verprolin-homologous protein (WAVE) (3, 4). Rho-GTPase activation is mediated by guanine nucleotide exchange factors (GEFs), which share common motifs: the Dbl-homology (DH) domain, which mediates nucleotide exchange (5), and the pleckstrin homology (PH) domain, which targets proteins to membranes and mediates protein–protein interactions (6). Dock1 (Dock180)–related proteins are a new family of Rho-GEFs that lack the DH/PH domains. Instead, Dock family proteins are characterized by two evolutionarily conserved protein domains, termed Dock homology regions 1 and 2 (DHR-1 and DHR-2, respectively) (7). However, the precise functions of the DHR domains are poorly understood. In mammals, there are 11 Dock1-related proteins (Dock1–11). We previously reported that one of the new Rho-GEFs, Dock3, also known as MOCA (modifier of cell adhesion protein), is specifically expressed in the central nervous system (CNS) and induces membrane spreading by activating Rac1 (8).
Neurotrophins are a small family of evolutionarily well-conserved neuropeptides that function in neural cell survival, development, and vertebrate CNS function (9, 10). Neurotrophins, such as brain-derived neurotrophic factor (BDNF), bind to two classes of receptors, the Trk receptor tyrosine kinase family (TrkA, TrkB, TrkC) and the low-affinity receptor p75 (p75NTR), leading to complex functional interactions (11, 12). Recent studies have demonstrated that neurotrophins play important roles during gastrulation, in the differentiation of hepatic stellate cells, and in neurulation, through the regulation of Rho-GTPases (9, 13, 14). Considering their relatively ubiquitous expression patterns, it is conceivable that Dock family members, in combination with neurotrophins, could be involved in the development and function of a variety of organs (15–17).
Here, we report that the atypical Rho-GEFs Dock1–4 share key amino acids within the DHR-2 domain that are critical for catalytic activity, and furthermore, that they bind directly to WAVE proteins through the DHR-1 domain. Moreover, we provide both in vitro and in vivo evidence that neuron-specific Dock3 plays a critical role in the membrane trafficking of WAVE proteins and also participates in axonal outgrowth in the adult CNS as an essential downstream component of BDNF-TrkB signaling.
Identification of Critical Residues Involved in GEF Catalytic Activity.
To identify residues critical for Rac1 activation, we constructed several Dock3 DHR-2 domain deletion mutants (Fig. 1A) and measured their catalytic activity with a GST-CRIB assay (Fig. 1B). All of the deletion mutants failed to activate Rac1 (Fig. 1B), indicating that amino acids 1358–1375 are required for Dock3-mediated GEF activity. We next introduced single alanine mutations into each of the 18 DHR-2 domain amino acids within full-length Dock3 and found that mutation at F1359, Y1360, G1361, Y1373, or V1374 completely abolished Rac1 activation (Fig. 1C) without affecting its ability to interact with Rac1 (Fig. 1D). Because the DHR-2 domain is highly conserved among Dock1–4 (Fig. 1A), the five single alanine substitutions corresponding to those found in Dock3 were introduced into Dock1, Dock2, and Dock4. All of the mutations drastically reduced Rac1 activation (Fig. S1), demonstrating that these five amino acids of the DHR-2 domain are critical for GEF catalytic activity in all Rac-specific Dock family members.
Identification of residues critical for the catalytic activity of Dock family members. (A) Domain organization and sequence alignments of Dock1–4. (B) (Left) Cos-7 cells were transfected with Dock3 deletion mutants. Lysates were subjected to a GST-CRIB assay. (Right) Quantitation of GTP-Rac. (C) Cos-7 cells were transfected with the indicated alanine-substitution mutants of Dock3. Lysates were subjected to a GST-CRIB assay. (D) Cos-7 cells were transfected with the indicated alanine-substitution mutants of Dock3. Lysates were incubated with GST-Rac and glutathione-Sepharose. Bound proteins were subjected to immunoblot analysis with anti-Dock3 antibody. (Lower) Coomassie Brilliant Blue (CBB) staining of GST-fusion proteins used in this experiment.
Dock3 Regulates Axonal Outgrowth.
To evaluate whether Dock3 induces axonal outgrowth, we transfected primary cultured hippocampal neurons with plasmid encoding Dock3. Overexpression of Dock3 significantly stimulated axonal outgrowth compared with the control (Fig. 2 A and B). As neurotrophic factors such as BDNF may also regulate Rac1 activation (18), we next examined whether Dock3 and BDNF have a synergistic effect on axonal outgrowth. Overexpression of wild-type (WT) Dock3 increased BDNF-mediated axonal outgrowth (Fig. 2 A and B), whereas Dock3 siRNA for downregulating endogenous Dock3 inhibited the effect of BDNF (Fig. 2B). Combinatorial siRNA to Dock1–4 decreased the baseline axon length (Fig. 2B). In addition, Dock3Y1360A and Dock3Y1373A also inhibited the effect of BDNF (Fig. 2B). BDNF-mediated axonal outgrowth and Rac1 activation were observed in cultured neurons from WT and p75NTR KO mice, but not from TrkB KO mice (Fig. S2). Trk receptor-specific inhibitor K252a and overexpression of dominant-negative Rac1 (Rac1 N17) suppressed BDNF-mediated axonal outgrowth (Fig. S2). Furthermore, we found that Dock3 is expressed in retinal ganglion cells (RGCs) and has a synergistic effect with BDNF on axonal outgrowth in cultured RGCs (Fig. S3). In retinal explant cultures, Dock3 protein was concentrated in growth cones (arrows in Fig. 2C) and was diffuse in cytoplasm (control panel in Fig. 2C). However, BDNF treatment rearranged Dock3 staining to the cell periphery (arrowheads in Fig. 2 C and D). These data demonstrate that Dock3 act in concert, upstream of Rac1, to promote axonal outgrowth through TrkB receptor signaling.
Dock3 enhances BDNF-mediated axonal growth. (A) Hippocampal neurons were transfected with Dock3 and cultured in the presence or absence of BDNF for 3 days. (Scale bar, 20 μm.) (B) Hippocampal neurons transfected and treated as shown at the x axis were fixed at 3 days in vitro, and axon length was measured. n = 30 per experimental condition. Data are mean ± SEM of three independent experiments. *P < 0.05, **P < 0.01. (C) Expression of Dock3 in retinal explant cultures. (Upper) Dock3 expression in growth cones (arrows). (Lower) High magnification of growth cones. Arrowheads indicate Dock3 recruitment to plasma membrane after BDNF treatment. (Scale bars, 50 μm in upper and 10 μm in lower.) (D) Ratio of growth cones in which Dock3 was recruited to plasma membrane. Data are mean ± SEM; n = 20 for each experimental condition. *P < 0.01.
Interaction of Dock3 and Fyn at the Growth Cone.
One consequence of the presence of BDNF in neurons is the activation of Fyn and its association with the TrkB receptor (19). Indeed, BDNF induced Fyn activation via phosphorylation at Y416 in primary cultured hipocampal neurons (Fig. 3A). Because the proline-rich motif of Dock3 binds to SH3 domain-containing proteins (8), we next examined whether Fyn, which also possesses an SH3 domain, interacts with Dock3. A GST-fusion protein of the proline-rich Dock3 C terminus (amino acids 1773–2028) coprecipitated Fyn in lysates of mouse brain as well as Fyn-transfected Cos-7 cells (Fig. 3B). In addition, a His-tag pull-down assay in Cos-7 cells transfected with His-tagged Dock3 together with WT Fyn, constitutively active FynY528F, or ΔSH3 FynY528F (20), confirmed the SH3 domain requirement and preferential binding to the active form of Fyn (Fig. 3C). In contrast, Fyn failed to bind to Elmo (21), which interacts with Dock1–4 and enhances their GEF activities (Fig. S4). Thus, the BDNF/TrkB-dependent activation and association with Fyn is specific. Consistent with the activated TrkB association with Fyn and interaction with Dock3, Dock3 translocated from cytosol to the membrane in SY5Y cells transfected with TrkB and FynY528F in the presence of BDNF, but not in cells transfected with TrkB and ΔSH3 FynY528F (Fig. 3D). In addition, BDNF-treated retinal explants exhibit colocalization of Dock3 and Fyn at the peripheral regions of the growth cone (arrowheads in Fig. 3E). These results are consistent with a model whereby BDNF-TrkB signaling induces the formation of a protein complex of Dock3 at the plasma membrane (Fig. 2 C and D). We further constructed a mutant Dock3 lacking Fyn binding domain (Δ1773–2028) and found that this mutant failed to stimulate BDNF-induced axonal outgrowth (Fig. 3F).
BDNF induces direct binding of Dock3 and Fyn in the growth cone. (A) Hippocampal neurons were transfected with WT Fyn and stimulated with BDNF for the indicated times. Lysates were subjected to immunoblot analysis with anti-FynpY416 or total Fyn antibodies. (Lower) expression levels of phosphorylated Fyn. Data are mean ± SEM of three independent experiments. *P < 0.05. (B) Lysates from mouse brain and Cos-7 cells transfected with WT Fyn were incubated with a GST-fusion protein of the Dock3 proline-rich domain. Bound proteins were subjected to immunoblot (IB) analysis with an anti-Fyn antibody. (Lower) Coomassie Brilliant Blue (CBB) staining of the GST-fusion proteins used in this experiment. (C) (Left) Schematic diagram of the WT and mutant Fyn constructs used in this assay. (Right) Lysates from Cos-7 cells transfected as shown at the top of the images were subjected to a His-tag pull-down assay with antibodies against Fyn and Dock3. (D) SY5Y cells were transfected with TrkB and FynY528F or ΔSH3 FynY528F and treated with BDNF. Arrowheads indicate colocalization of Dock3 (green) and WAVE1 (red) at the peripheral region. Arrow indicates a nontransfected cell. (Scale bar, 20 μm.) (E) Colocalization of endogenous Dock3 (green) and Fyn (red) in growth cone of retinal explant cultures after BDNF treatment. (Scale bar, 10 μm.) (F) Hippocampal neurons transfected and treated as shown at the x axis were fixed at 3 days in vitro and axon length measured. n = 30 for each experimental condition. Data are mean ± SEM of three independent experiments. *P < 0.05.
Direct Interaction of Dock3 and WAVE Proteins.
Because WAVE proteins play a major role in Rac-induced actin dynamics, including actin nucleation and polymerization (3, 4), we speculated that they could be involved in Dock3-mediated axonal outgrowth. To investigate the possibility that WAVE1 can directly bind to Dock3, we performed a His-tag pull-down assay using WT Dock3 or several Dock3 truncation mutants. We found that Dock3 directly bound to WAVE1 at the DHR-1 domain (Fig. 4A). We next constructed a mutant that lacks the DHR-1 domain (ΔDHR-1) and determined that this mutant also failed to bind to WAVE1 (Fig. 4B). We further confirmed that the DHR-1 domain of Dock3 was required to mediate WAVE1–3 binding (Fig. 4C). Indeed, this interaction between Dock and WAVE proteins can be generalized (Fig. S5). In addition, we demonstrated that ΔDHR-1 failed to stimulate BDNF-induced axonal outgrowth in hippocampal neurons (Fig. 4D). We next prepared both WT and two mutant forms of WAVE1 constructs and found that one mutant that lacks the WAVE-homology domain (WHD) failed to bind to WT Dock3 (Fig. 4E). Based on the preceding data, we hypothesized that membrane targeting of Dock3 may regulate the intracellular localization of WAVE. To assess this possibility, we transfected SY5Y cells with WT Dock3 and subjected them to immunocytochemistry. Overexpression of WT Dock3 did not change the intracellular localization of WAVE1 (Fig. 4F). In contrast, overexpression of farnesylated Dock3 (F-Dock3, a membrane-targeted form of Dock3) translocated WAVE1 from the cytoplasm to the peripheral regions (arrowheads in Fig. 4F). Taken together, these results suggest that the DHR-1 domain of Dock family proteins mediates direct binding to WAVE proteins leading to colocalization at the cell periphery and axonal outgrowth.
Phosphorylation of Dock3 regulates its interaction with WAVE. (A) (Left) schematic diagram of the WT and mutant Dock3 constructs used in this assay. (Right) Lysates from Cos-7 cells transfected as shown at the top of the images were subjected to a His-tag pull-down assay with antibodies against WAVE1 and Dock3. (B) Lysates from Cos-7 cells transfected as shown at the top of the images were subjected to a His-tag pull-down assay with antibodies against WAVE1 and Dock3. (C) Lysates from Cos-7 cells transfected as shown at the top of the images were subjected to a His-tag pull-down assay with antibodies against myc-tag, WAVE1, WAVE2, and WAVE3. (D) Hippocampal neurons transfected and treated as shown at the x axis were fixed at 3 days in vitro, and axon length was measured. n = 30 for each experimental condition. Data are mean ± SEM of three independent experiments. *P < 0.05. (E) (Left) Schematic diagram of the WT and mutant WAVE1 constructs used in this assay. (Right) Lysates from Cos-7 cells transfected as shown at the top of the images were subjected to a His-tag pull-down assay with antibodies against Dock3 and WAVE1. (F) SY5Y cells transfected with WT Dock3 or F-Dock3 were probed with antibodies against WAVE1 (red) and Dock3 (green). Arrowheads indicate WAVE1 protein at the peripheral region. The arrow indicates a nontransfected cell. (Scale bar, 10 μm.) (G) Lysates from Cos-7 cells transfected with WT Dock3 or F-Dock3 were subjected to immunoblot analysis with an anti-Dock3 antibody. Arrow indicates phosphorylated Dock3. (H) (Upper) Relative expression levels of phosphorylated Dock3 to total Dock3. (Lower) Lysates from Cos-7 cells transfected as shown at the bottom of the images were subjected to a His-tag pull-down assay. Bound and unbound proteins were subjected to immunoblot analysis with an anti-Dock3 antibody. Arrow indicates phosphorylated Dock3.
We also found a strong enhancement of the Dock3 upper mobility band (arrow in Fig. 4G) in Cos-7 cells transfected with F-Dock3 but not with WT Dock3 (26 ± 6% and 2 ± 1% of total Dock3, respectively). Consistent with the upper mobility band representing a phosphorylated form of Dock3, the mobility shift was eliminated by phosphatase treatment (Fig. 4G). We next examined the effect of Dock3 phosphorylation on its ability to bind WAVE. Cos-7 cells were transfected with His-tagged WAVE1 and F-Dock3 and subjected to a pull-down assay. Immunoblot analysis revealed that WAVE1 binds to the unphosphorylated form of Dock3 more effectively than to the phosphorylated form (Fig. 4H). Thus, the Dock3/WAVE1 complex may dissociate upon Dock3 phosphorylation, leading to spatially restricted actin dynamics through WAVE signaling.
Promoting Axonal Outgrowth in Adult CNS by Modulating Dock3 Activity.
To investigate the effects of Dock3 in vivo, we generated transgenic (Tg) mice overexpressing WT Dock3 under control of the actin promoter. Tg mice showed high expression levels of Dock3 in many tissues, especially in the optic nerve (∼5.6-fold) and retina (∼2.3-fold; Fig. S6A), but the structure of such tissues were normal (Fig. S6 B and C). Therefore, we prepared retinal explants from WT and Tg mice and examined the effect of Dock3 on axon length. Quantitative analysis revealed that axon length was clearly greater in Tg mice than in their WT littermates (Fig. 5A). Furthermore, Dock3 and BDNF exerted synergistic effects on axonal growth, as observed in vitro (Fig. 2 A and B). These results suggest that axonal outgrowth is promoted in Dock3 Tg mice. To explore this possibility, we used the optic nerve microcrush model and investigated the extent of axonal outgrowth 2 weeks after injury by staining with GAP43 antibody (22). WT mice subjected to nerve crush showed >40 axons extending 200 μm from the injury site, and half this number extended 500 μm. In contrast, Tg mice had, on average, >80 axons extending 200 μm and >60 axons extending 500 μm beyond the lesion site (Fig. 5B). Immunohistochemical analysis of Dock3 and WAVE1 in injured optic nerves revealed that their coexpression was hardly detectable in WT mice, but was clearly increased in regenerating axons in Tg mice (Fig. 5C). We next examined the levels of Dock3 and WAVE1 proteins in optic nerves by immunoblotting (Fig. S7). Dock3 protein was reduced in injured WT optic nerves (decreased to ∼10% of control), but this reduction was less severe in Tg mice. In both WT and Tg mice, WAVE1 protein was less abundant after the injury (reduced to ∼60%). Whereas in the membrane fraction of crushed optic nerves, Dock3 and WAVE1 expression levels in Tg mice were significantly higher than WT mice (Fig. 5D and E). We also examined the expression of TrkB and Fyn in injured optic nerves, but their expression levels in Tg mice were not significantly altered compared with those in WT mice (Fig. S8). Thus, overexpression of Dock3 does not affect the expression levels of its binding partners, but may induce axonal outgrowth through effective membrane recruitment of WAVE1.
Overexpression of Dock3 induces axonal regeneration in vivo. (A) (Upper) Retinal explants from WT and Dock3 Tg mice cultured in the presence or absence of BDNF were fixed and labeled with phalloidin at 2 days in vitro. (Lower) Axon length was measured and quantified. Data are mean ± SEM, n > 80 axons for each group. *P < 0.05. (Scale bar, 100 μm.) (B) (Upper) GAP43-labeled axons in the optic nerve proximal to the injury site (dotted line) 2 weeks after nerve surgery. Arrowheads indicate regenerating axons. (Lower) Regenerating axons from lesion site were measured and quantified. Data are mean ± SEM for six independent experiments. *P < 0.05. (Scale bar, 50 μm.) (C) Immunostaining of the optic nerves proximal to the injury site (dotted line). Arrowheads indicate colocalization of Dock3 (green) and WAVE1 (red) in the regenerating axons. (Scale bar, 20 μm.) (D) Immunoblot analysis of Dock3 and WAVE1 in the membrane fraction of optic nerve 2 weeks after nerve surgery. (E) Expression levels of Dock3 and WAVE1 in the membrane fraction of normal and injured optic nerves were quantified. Data are presented as means ± SEM of three independent experiments. *P < 0.05.
In the present study, we found that Dock1–4, which are atypical members of the Rho-GEF family, share several conserved amino acids in their DHR-2 domains that are required for GEF activity. In addition, Dock1–4 bind directly to WAVE1–3 via their DHR-1 domains, and this is disrupted when Dock1–4 become phosphorylated. We further showed that Dock3 forms a protein complex with Fyn and WAVE1 at the plasma membrane downstream of TrkB. Finally, we demonstrated that overexpression of Dock3 increases WAVE1 expression levels in the plasma membrane and promotes optic nerve regeneration in vivo. Taken together, our results suggest a unique mechanism for axonal outgrowth through which Dock-GEFs recruit WAVE proteins to specific sites within cells and induce spatially restricted actin dynamics in the CNS (Fig. 6).
Proposed role of Dock3 in BDNF-mediated axonal outgrowth. BDNF-TrkB signaling induces Fyn phosphorylation and stimulates membrane recruitment of the Dock3/WAVE complex. Dock3 is then able to activate Rac-GDP (inactive form). Rac-GTP (active form) and WAVE are dissociated from phosphorylated Dock3 and stimulate actin reorganization, leading to axonal outgrowth.
BDNF/TrkB signaling is important for a variety of CNS developmental processes including synaptic pruning (23, 24). In addition, Rho-GTPase signaling can affect both spine structure and synaptic function (25, 26). In this study, we found that treatment of hippocampal neurons with BDNF enhances Rac1 activation and neurite outgrowth. It is therefore possible that Dock-GEFs mediate multiple BDNF/TrkB functions, including the establishment of long-term potentiation. On the other hand, loss of Dock3 leads to sensorimotor impairments and structural changes, including axonal swellings, but had no effects on life span or fertility (15). These relatively mild phenotypes are reasonable, considering the redundant catalytic sequences found in the DHR-2 domains of Dock1–4. Recent studies have revealed that a Val66Met polymorphism in human BDNF is involved in the pathogenesis of attention-deficit/hyperactivity disorder (ADHD) (27–29). Interestingly, a pericentric inversion breakpoint in the DOCK3 gene has been described in ADHD patients (30). Thus, further study is required to determine the full implications of the Dock-GEFs in BDNF-associated development, adult physiology, and disease.
Dock3 overexpression induced optic nerve regeneration after injury without affecting expression levels of its binding partners. For example, WAVE1 expression level after optic nerve injury was decreased to ∼60% in both WT and Dock3 Tg mice. However, WAVE1 expression was increased in the membrane fraction and was coexpressed with Dock3 in the regenerating axons. Thus, the tight regulation of Rac1-GDP/Rac1-GTP cycling and effective membrane recruitment of WAVE proteins by Dock3, rather than prolonged activation of Rac1 or WAVE proteins (31–33), may be required for axonal growth via actin polymerization. Our present findings support the notion that neurons have to intrinsically up-regulate the necessary growth-associated molecules to extend an axon (34, 35). On the other hand, recent studies have shown that glial scarring and several myelin inhibitors block axonal growth following CNS injury (35, 36). Thus, overexpression of Dock-GEFs may have a synergistic effect in combination with suppression of glial scarring and myelin-associated inhibitory signaling.
Lack of axonal regeneration in the adult CNS is one of the most important issues to be resolved in various neurodegenerative disorders. For example, glaucoma is characterized by a slow progressive degeneration of optic nerve axons. Thus, Dock/WAVE complexes and their related binding partners may be possible therapeutic targets in multiple forms of glaucoma that otherwise lead to severe visual impairment. We are presently investigating these issues by crossing Dock3 Tg mice with glutamate transporter knockout mice, which are the first animal models of normal tension glaucoma (37). Thus, further studies are required to explore the full potential of Dock-GEFs that could be used for effective regeneration therapy.
Experimental Animals.
Experiments were performed using p75NTR knockout and TrkB × hGFAP-cre knockout (TrkB KO) mice in accordance with the Tokyo Metropolitan Institute for Neuroscience Guidelines for the Care and Use of Animals. The TrkB deletion was confirmed in the hippocampus of the TrkB KO mice (23). A Tg construct containing the CAG promoter, Dock3 coding sequence (GenBank accession no. NM_153413), and a polyadenylation signal was used to generate Dock3 Tg mice. The founder mice were generated by injecting the transgene into fertilized C57BL/6 eggs. RGCs were retrogradely labeled with Fluoro-Gold (Fluorochrome) as previously described (38).
Cell Culture.
Primary cultured hippocampal neurons (39) and retinal explants (22) were prepared from E16 mice. In some experiments, they were stimulated with BDNF (5 or 50 ng/mL; Alomone Labs).
Plasmids and siRNA Transfection.
WAVE1–3 plasmids were provided by T. Takenawa (40). Elmo2 and GST-CRIB plasmids were provided by H. Kato and M. Negishi (21). Rac and Dock1 plasmids were provided by M. Matsuda (41). Dock3, Fyn, and WAVE1 fragments were PCR-amplified from full-length cDNAs and expressed as His-tagged proteins. Alanine substitutions were generated with the PrimeSTAR Mutagenesis Basal Kit (Takara). RNA oligomers containing 21 nucleotides for RNA interference for Dock1–4 were synthesized in the sense and antisense directions (Dock1: 5′-GGAAGUCACCACAACGCUUUU-3′; Dock2: 5′-GCAUCUCA CGCUACAGAUUUU-3′; Dock3: 5′-GCAGAUCAGUGAACGGUUUU-3′; Dock4: 5′-GCAAGAGUGUGGCCAGAAAUU-3′) (JBioS). Transfection of siRNAs and plasmids was performed using the Nucleofector System (Amaxa) or Lipofectamine Plus (Invitrogen).
Pull-Down Assay.
His-tagged proteins were purified from Cos-7 cell lysates with TALON resin (BD Biosciences) for 20 min at 4 °C with gentle agitation. The protein levels of Rac-GTP were measured by affinity precipitation using the GST-CRIB of PAK1. Bacterial GST-fusion proteins were incubated with lysates from Cos-7 cells or mouse brains. The precipitated samples were subjected to SDS-PAGE followed by immunoblot analysis (8) with the following antibodies: Fyn, phospho-Fyn (Tyr416) and WAVE1 were obtained from BD Biosciences; WAVE2 and WAVE3 were obtained from Santa Cruz.
Immunostaining.
SY5Y cells, retinal explants, sections of retina, and optic nerves were incubated with anti-Dock3 (1:200), anti-WAVE1 (1:200), and anti-GAP43 (1:1,000; Chemicon) antibodies. Cy2-conjugated donkey antirabbit IgG or Cy3-conjugated donkey antimouse IgG were used as secondary antibodies. F-actin was visualized with rhodamine-labeled phalloidin (Invitrogen).
Optic Nerve Injury.
Mice were anesthetized with sodium pentobarbital before optic nerve crush. Optic nerves were exposed intraorbitally and crushed about 0.5–1.0 mm from the posterior pole of the eyeball with fine surgical forceps for 5 s (22). Fourteen days after surgery, axonal outgrowth was quantified by counting GAP43-positive axons that crossed a virtual line parallel to the lesion site at 200 μm and 500 μm distal to the lesion site. Protein expression levels in the lesion site were measured by immunoblot analysis with antibodies against Dock3 and WAVE1–3. Membrane fraction was prepared as previously described (42).
Image Analysis and Statistics.
To measure axon length, the longest axon of each neuron was traced and calculated using National Institutes of Health ImageJ (version 1.38). Approximately 50 neurons with axons were scanned using a DP70 CCD camera (Olympus). Data are presented as mean ± SEM. For statistical analyses, a two-tailed Student's t test was used. Values of P < 0.05 were regarded as statistically significant.
We are grateful to T. Takenawa (Kobe University) and H. Kato, M. Negishi, and M. Matsuda (Kyoto University) for reagents. We thank A. Kimura, K. Nakamura, and K. Nishimura for technical assistance, and R. McKay for comments on the manuscript. This study was supported by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (to K.N., C.H., and T.H.); Ministry of Health, Labour, and Welfare of Japan; Uehara Memorial Foundation; Naito Foundation; Suzuken Memorial Foundation; Daiwa Securities Health Foundation; Takeda Science Foundation; and Japan Medical Association (to T.H.).
1To whom correspondence should be addressed. E-mail: harada-tk{at}igakuken.or.jp.
Author contributions: K.N. and T.H. designed research; K.N., C.H., C.T., and X.G. performed research; K.N., C.T., H.K., and L.F.P. contributed new reagents/analytic tools; K.N., C.H., X.G., L.F.P., and T.H. analyzed data; and K.N., L.F.P., and T.H. wrote the paper.
This article contains supporting information online at www.pnas.org/cgi/content/full/0914514107/DCSupplemental.
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You are going to email the following Dock3 induces axonal outgrowth by stimulating membrane recruitment of the WAVE complex
Kazuhiko Namekata, Chikako Harada, Choji Taya, Xiaoli Guo, Hideo Kimura, Luis F. Parada, Takayuki Harada
Proceedings of the National Academy of Sciences Apr 2010, 107 (16) 7586-7591; DOI: 10.1073/pnas.0914514107

redpajama_set_name: RedPajamaCommonCrawl


text:
Aamir thanks Akshat, Abhinay for 'Delhi Belly' success
Jul 7, 2011 IANS
Mumbai, July 7 (IANS) "Delhi Belly" has rocked the box office and an overhwlemd Aamir Khan, the producer of the adult comedy, gives maximum credit to writer Akshat Verma and director Abhinay Deo for delivering such an entertaining film.
Aamir enjoyed the public reaction in person by sneaking into different theatres in the city.
"Well, I am very happy to see that people are loving this film so much. I am going from theatre to theatre to see public reaction. It's amazing to see houseful audiences laughing, whistling in the halls," Aamir told reporters at the success bash here Wednesday night.
"The work that Akshat, Abhinay has done is praise worthy and the actors too pulled off their vision very well. I am thankful to them for giving such a wonderful film," he added.
If the film is produced by Aamir, the youth-centric bold drama stars his nephew Imran in the lead role along with Vir Das and Kunal Roy Kapoor. Made at a budget of Rs.25 crore the film triumphed in the opening weekend by grossing over Rs.26 crore.
At the bash, Aamir walked up to every table and introduced all crewmembers and thanked them personally for making the film so successful.
Buoyed by the success of "Delhi Belly", Aamir now wants to experiment with more unique ideas.
"I have always experiment with films so whenever I venture for films I make sure I don't repeat myself. Every time I want to challenge myself doing unique films," said the 46-year-old filmmaker who produced films like "Peepli Live", "Dhobi Ghat", "Taare Zameen Par", "Jaane Tu... Ya Jaane Na" and "Lagaan".
The invitees at the party were friends and families of Aamir as well as the crew members of the film.
Actor Anil Kapoor and screenplay writer Prasoon Joshi were spotted, but they only came to meet Aamir and didn't interact with the media.
Surprisingly Aamir's filmmaker wife Kiran Rao was also missing. When asked about her, Aamir said, "She is not in town."
Click the Movie button below for more info:
Delhi Belly
Aamir Khan Pictures


text:
Kurohime may refer to

Mount Kurohime, a mountain in Nagano Prefecture, Japan
Kurohime Station, a train station in the vicinity of the mountain
Mahō-tsukai Kurohime, a manga serialized in Monthly Shonen Jump

redpajama_set_name: RedPajamaWikipedia


British manufacturer Muraspec is launching a new range of wallcoverings at Sleep, stand M7A. The 20oz Type II wallcoverings have been specifically designed and manufactured for the hospitality industry, inspired by a growing need in the sector for beautiful textile effects in sophisticated colour palettes. The exciting new collection is texture-based with fabric-style embosses and weave prints, and is available in a range of stylish colours in matt and lustre finishes.


TESOL professionals are often not involved in the decision-making that drives English language policy, high-stakes assessment, materials development, research, and practice. To change that, in 2017 TESOL International Association spearheaded the Summit on the Future of the TESOL Profession. The summit helped shape a strategic conversation intended to set a course for the future.
The ideas, recommendations, conclusions, and outcomes conceived at the summit have been synthesized into a Action Agenda for the Future of the TESOL Profession. (An executive summary is also available).
The agenda is intended to serve as a guiding framework for the TESOL profession at the local, regional, national, and international levels.
empower TESOL professionals and the English learners they serve.
For more information about the Action Agenda, please contact TESOL Advocacy.


You can use Gmail to send and store scanned documents. While there isn't a direct way to send scanned documents to your Gmail account, you can scan the documents to your computer and attach them to emails in Gmail. Then, you can just send the documents to your coworkers, clients and employees. You can also send the emails to yourself as an impromptu document archiving solution.
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I found myself in covent garden after work with the urge for pizza and for something new. I decided to fire up my tastecard and found Fire and Stone, a Spacious restaurant serving creative pizzas and pasta in a casual cafe-style setting.
There are no halal meat options so it was veg for me!
Just got one starter, RUSTIC POLENTA CHIPS £4.45, Crisp fried with fresh rosemary & tomato salsa. I loved this dish! I think i can say it was actually one of the best chips i have had, the accompanying salsa was great.
Might be the best chips I've had!
For my pizza i got the Mumbai pizza, Two naan pizza bases topped, red onion, chilies and spinach paneer served with poppadoms, mango chutney & tzatiki. This pizza comes with chicken, so I asked for no chicken on mine.
However, when I first got the pizza (which did take around 20mins to arrive) I noticed one piece of chicken on it, i told the waiter who promptly apologised and said he would order me another and make sure it's done right.
When it finally arrived, well, it's basically some cheap pitta bread made into a pizza. It was okay.. Would i have it again? No, note to self, if you want a pizza, then get a pizza!
We also got a " Melbourne", Chunks of brie, roasted butternut squash, balsamic red onions, mozzarella, topped with rocket & pumpkin seeds, drizzled with a balsamic glaze, £11.50. This actually tasted like a pizza! Yay. It was a simple but nice pizza i liked the sweetness of the balsamic red onions and glaze.
For dessert, we got HOMEMADE CHOCOLATE BROWNIE, £6.25 , With chocolate sauce & Madagascan vanilla ice cream. Really soft and gooey, i liked this dessert.
Also got some CHURROS, Crispy cinnamon coated churros strips with Nutella & chocolate sauce dips. £5.25.
Because of the order mix up, my Indian pizza was taken off the bill and we also got 50% off as i used my tastecard. So the total came to very low £15, for one starter, 2 pizzas and 2 desserts!
Would i go back? Absolutely, armed with my tastecard, I'd definitely get those chips and that dessert again.
Hey Buddy!, I found this information for you: "Fire and Stone". Here is the website link: http://halalfoodguy.co.uk/fire-and-stone/. Thank you.


text:
FAITH DOING JUSTICE
Vol 21 No 3
In defence of people-smuggling
During the brief storm caused by Shadow Minister for Immigration and Citizenship, Scott Morrison's remarks on the recent asylum seeker funerals, another senior Liberal praised his compassion, claiming he was deeply affected by the sufferings people smugglers had caused asylum seekers.
I am delighted to accept this testimony to Morrison's compassion for asylum seekers. But, even if this compassion is sincere, the implicit argument that asylum seekers merit sympathy because they are the passive victims of people smugglers is pernicious.
It is usually put in this form. Credulous asylum seekers are lured by avaricious people smugglers to travel on unsafe boats to Australian territory. Fellow-feeling with asylum seekers demands that this risk to life and health must therefore be stopped by preventing and penalising travel by boat.
This argument assumes that death at sea in an unsafe boat is the greatest peril that asylum seekers have to fear, that they are the passive and deluded victims of people smugglers, and that their lives will benefit if people smugglers are neutered. None of these assumptions is true.
Asylum seekers walk with death as their shadow. Persecution in your homeland and surrounding nations means living among people who will rejoice in your death, others who will not lift a finger to keep you or your family alive, and a society in which your humanity is valued less than animals.
If you pray with a group of asylum seekers, they will ask you to remember their dead relatives and friends and those who risk death along the way.
The story of asylum seekers has always been of fortunate and determined survivors and the unknown dead. Many Jews died trying to leave Germany. Some estimate that more than a third of the hundreds of thousands who fled from Vietnam after 1975 were killed by pirates or sank while at sea. Many Cambodians died in minefields or where shot by paramilitary when escaping into Thailand.
Villagers from El Salvador, harried by their armed forces and hunted out of their homes, died at the guns trained on them from both sides of the Rio Lempa. And yet they all continued to flee.
Asylum seekers have also always needed help to make their journey to safety. Even Joseph and Mary are often depicted with a young guide as they flee into Egypt. Many Jewish asylum seekers were given shelter and helped to cross borders by ordinary families and by religious communities.
Our people smugglers may be seen as distinctive in that they charge high prices for their troubles. But asylum seekers have always relied on people who exploited them. Chances are that even the legendary donkey on which Mary and Jesus rode to Egypt was hired at an extortionate rate.
Certainly, asylum seekers from behind the Iron Curtain, Cambodians fleeing into Thailand, Afghans escaping the Taliban and Vietnamese fleeing from Vietnam all needed help to escape. They often feared their helpers, but had no other options. They were prepared to pay over the odds for the opportunity to save their lives and retain their dignity as human beings.
In Australia most on-shore asylum seekers have been found to be refugees. This is testimony that they had the courage and inner resource to escape persecution in their own countries, to risk their lives and those of their families by setting out on a long journey, including on an overcrowded boat, in order to find protection. For them people smugglers are minor attendants in death's court.
If we are to sympathise with asylum seekers we owe it to them to listen to their story, to be moved to anger at the conditions that forced them from their own country, to admire their courage and freedom of spirit, to grieve for those who died at each point of the journey, and to ensure that those who need protection are offered it without need of people smugglers.
Measures like pushing boats away, keeping people in detention and dumping them on Nauru don't flow naturally from sympathy for asylum seekers. They are the natural expressions of fear and antipathy. Of course, like the legendary headmaster who caned boys savagely while feeling more hurt than they were, it is possible in good conscience to feel sympathy and to support barbarous deeds. But in the case of asylum seekers, this attitude is condescending. It pretends that we can know their predicament better than they know it themselves, and that we can address the ills they suffer by further unmerited assault on their dignity.
In a fallen world and so, mercifully, not in Australia, it is also conceivable that people might feign sympathy for the suffering of asylum seekers at the hands of people smugglers in order to win support for their proposal to prevent asylum seekers from coming to Australia by boat, come what may. In that case the expression of sympathy would be canting humbug, a grimace to mask the brutality of one's attitudes and actions.
Either way, neither asylum seekers nor the rest of us should have to put up with this nonsense.
Andrew Hamilton is the consulting editor of Eureka Street.
Recent articles by Andrew Hamilton.
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Topic tags: Andrew Hamilton, people smugglers, Scott Morrison, asylum seeker funerals
SUPPORT RESPECTFUL CONVERSATIONS IN A TIME OF DIVISION
If there's one thing that the recent election campaign and its outcome demonstrated, it's the depth of the divisions that exist in our Australian community.
Our politics is focused on point-scoring, personalities, and name-calling across party lines. The media, for the most part, don't help, driven by the 24-hour news cycle and the pursuit of advertising dollars into a frenzy of click-bait and shallow sensationalism.
What does it mean to be an Australian in times like these? What are the values that unite us?
Eureka Street offers an alternative. It's less a magazine than a wide ranging conversation about the issues that matter in our country and our world; a conversation marked by respect for the dignity of ALL human beings.
Importantly, it's a conversation that takes place in the open, unhindered by paywalls or excessive advertising. And it's through the support of people like you that it is able to do so.
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Existing comments
Instead of fear of the other, if fearful Australians and poll driven politicians had a modicum of the courage that asylum seekers have we would be a compassionate nation that welcomes the vulnerable. Particularly the vulnerable of our own making- from Afghanistan & Iraq.Thank you Andrew.
Dr Vacy Vlazna | 25 February 2011
The whole, "Can profiteers do good for refugees?" question should be banal after the mainstream film 'Schindlers list'. This historical hypothesis was thoroughly examined by Thomas Keneally and the answer popularised by Steven Spielberg. You would have thought that that would have been the final word on the matter.
martin spencer | 25 February 2011
A broad brush is a fine tool if one wants to paint a wide wall but such a brush with its weight of paint would drown valuable detail needing to be highlighted.
Andrew has wielded a broad brush with his unsubstantiated claim that "asylum seekers have always relied on people who exploited them" and, thus, he has smothered the truth.It is simply wrong to make such a dreadful claim.
There is absolutely no basis whatsoever for his bizarre claim which suggests every asylum seeker...Jews in flight from Hitler, Cambodians fleeing Pol Pot etc etc...had to pay "over the odds". That denies the reality and unselfish efforts of unknown thousands through the ages who were never motivated by money to go to their rescue, people willing to risk their own lives in the course of right or justice or mercy.
It's also pure supposition to assert that
"Chances are that even the legendary donkey on which Mary and Jesus rode to Egypt was hired at an extortionate rate". Yes, it's a captivating line, but that's all.The reality was likely very different indeed.If a four legged treasure could command an 'extortionate" price, who would risk riding it without a significant escort?Joseph and Mary's "young guide" was a guide, not an armed guard.
There are alternatives to smugglers and dangerous boats.A tidal wave of humanity is presently seeking to swirl out of Libya,Tunisia,Yemen, and other lands run by despots. But where are the voices of the world's national and religious leaders? When will the Pope speak up?
Brian Haill - Melbourne | 25 February 2011
There is a huge difference between refugees and those who deliberately enter the country illegally. People smugglers are criminal murderous scum. Emotionalism does not overcome logic.
Trent | 25 February 2011
Andrew, thank you for bringing your usual depth, complexity and compassion to a 'taboo' subject.
Anne | 25 February 2011
Thanks Andrew. I like the idea about overcharging for donkeys. But the headline suggests this would be a defense of the people smugglers themselves.
Comments by Trent in particular suggest that is precisely the debate we now need to entertain: are people smugglers all, invariably, 'murderous scum'?
Tom Clark | 25 February 2011
I really enjoyed this article. Portraying people smugglers as 'evil' and asylum seekers as passive 'victims' is simplistic and lazy does not help at all in seeking to understand the complex factors that cause people to flee their homes and countries. It also denies agency to asylum seekers which, in turn, allows policy makers to treat them as a faceless and homogenous mass.
Lia Kent | 25 February 2011
The situation in Europe, UK and Ireland after WW2 was parlous. To use the broad brush of Andrew - and risking the criticism of some commentators - the Australian government was able to take advantage of a situation where people were desperate (many for sake of their children) to get away as far as they could from lands that had seen centuries of conflict.
The push factor to leave was huge. The pull factor was the Australian government offering cheap transport to a peaceful and prosperous land. Push and pull factors operate in the case of refugees trying to get to Australia. Desperate situations call for desperate measures. Until nation-states (of all complexions)and the UN face the facts (persecution/discrimination/poverty/civil war etc) that turn citizens into refugees and do something about them, refugees, like the poor, will be with us for a long long time.
I don't defend people smugglers but I can understand how desperate people turn to them as, in their eyes, the only viable option.
People smuggling out of source countries, such as Sri Lanka and Afghanistan,is only possible through bribery and corruption of officials.
Politicians could try working for peace and against corruption instead of "stopping the boats".
Uncle Pat | 25 February 2011
Have you figured out how much they have to pay to come here? and how do they pay that? thse puzzle me.
If they go and live in Kabul with that amount of monies, they would be able to make a good living and that will contribute their nation in a very resonable way.
Corruption in Afghanistan is a well-known issue but the citizens themselves have the responsibility to correct their country.
Afghanistan is not a bad country anymore but the people have to start changing their lifestyle to suit a better situatiion and make their country good.
Australia has spent both moneys and life to make Afghanistan safe and become a better country - they must not forget that and they must keep their country well.
AZURE | 25 February 2011
I found myself nodding in agreement as I was reading your article, Andrew. While it is difficult for me to put myself in an asylum seeker's shoes, your perspective about the motivation of asylum seekers is in accord with what I can imagine and, in fact, learned through some contact I had with asylum seekers at Villawood some years ago.
Trent, I think you should re-read your very emotional statement and see the contradictions therein.
Erik H | 25 February 2011
'we owe it to them to listen to their stories'. yes Andrew and then to try to put on their shoes. Surely then we will speak from the heart, our own and that of the Gospel. Thank you Andrew for your compassion, understanding of situations and great way with words.
Anna C | 25 February 2011
It has to be agreed that any persons wishing to come to our country whether as asylum seekers or just as seekers for a better life for themselves or their families have an inalienable right to do so. That principle is enshrined in internationalo L-A-W.
But as Andrew points out, help from others to make their land fall is usually required. For those not at risk of their lives but waiting agonisingly in an immigration centre in Indonesia, and finally paying for help from criminal people smugglers,is a desperate act.
"Lie down with dogs - get up with fleas".
Andrew can not compare our boat-borne asylum seekers with Jews fleeing the Nazis in Germany or Salvadorians dodging bullets during their escape. This part of his commentary is dangerous and naive.
Claude Rigney | 25 February 2011
Trent. It is not "Illegal" to seek asylum in Australia. You illustrate the widespread ignorance which pervades this subject. Most of those who arrive by boat are found to be genuine refugees. They have broken no laws by seeking protection in Australia.
Mike Hopkins | 25 February 2011
I feel this comment is most just and compassionate - and long overdue. It takes someone of the calibre of Andrew Hamilton whose words I always read to put the focus where it should be. I thank God for his influence on this troubled country.
Carmel Moore | 25 February 2011
By virtue of its geography, Australia receives only a fraction of the number of refugees and asylum seekers who arrive in most developed countries in Europe.
So there is some puzzlement here in France that Australia is so unwelcoming given its vast spaces, its extraordinarily robust economy and the reputation Australians used to have for generosity.
Very instructive article. Thanks, Andrew.
Alan Austin | 25 February 2011
Dear Trent, whether now or in the past, there is often no difference between refugees and those who deliberately enter a country illegally. We are not talking here much of the time about people with a choice. How a country responds to refugees is a test of that country's basic understanding of how its people respect other humans.
Then again, there is a huge difference between refugees and those who deliberately stay in the country when they should have returned to Britain five years ago. It's called overstaying your visa. People smugglers are not criminal murderous scum, in fact murder is precisely what they are not committing as that would destroy their prime motive, which is to make money out of these vulnerable human beings. Murder is illegal in Indonesia, unless something has changed. Emotionalism, as you have just demonstrated in your argument, overcomes logic. A more interesting exercise is to follow a logical argument and figure out where the emotion is operating.
Can emotion ever be completely separated from the logic of an argument? For general reflection, it was the great and holy man Saint Benedict of blessed memory who required hospitality. Every Benedictine House has a guestroom. Sincerely, Desi.
Desiderius Erasmus | 25 February 2011
At last someone has exposed the hypocrisy of those who profess to be concerned about the plight of asylum seekers but instead of acknowledging their legitimate fears and entitlement to sanctuary shift the emphasis onto those 'evil people smugglers'. This article should be published in the mainstream press -say the Opinion Page in the Age. I am sure many people will welcome someone saying it as it is and reflecting what a lot of people think even if the polls show otherwise.
It's time to shape opinion and encourage people to think independently, not just to bathe in the convenient bias promoted by our political leaders.
Jacinta Heffey | 25 February 2011
Well said Andrew. Most of our loathing of people smugglers is shooting the messenger
Jim Jones | 25 February 2011
Australia is a place on this planet where human beings currently live well.We have a tradition of excellence in our fighting forces but we have grown soft and I doubt if confronted by a conflict in the future we could acquit ourselves sufficiently to repel an invader. We might not need young fit men and women now, but the sons and daughters of the asylum seekers we accept into our country now will be the defenders we will need in the future............... desperately!mark my words!
Jack Kennedy | 25 February 2011
Thank you for your comments. To carry the conversation further, I shall take up points made on two of the postings.
Azure suggests that the Afghan asylum seekers should have gone to Kabul where they could have worked to build up their country. The Afghan asylum seekers whom I know would have said, 'Would that we could!'
They flee because they are persecuted in their own country, and because even in Kabul the government either cannot or will not give them the protection against persecution that they need to live securely and to contribute to society. Would we have required the Jews fleeing Hitler to return to Germany in order to build a better society?
Claude Rigney says it is naive to compare the plight of the Jews and others with asylum seekers who are waiting in an immigration centre in Indonesia. From their perspective, I do not see the naivety. Like the Jews, they have fled in fear of a persecution that threatens their life and their human dignity. Like many of the Jews, in their flight they find themselves in a country and situation where they also are prevented from living with dignity. They believe the risk they will take to find their humanity protected. This is simply another step in their flight from persecution to hoped for safety.
The point at issue here is perhaps not the comparison with other groups, but the conditions under which they live in Indonesia, and therefore the reasonableness of their leaving it. As I have heard the story of life in Indonesia, it involves living in a poor nation which is not a signatory to the UNHCR Convention, and therefore with no commitment to protect refugees.
It involves also a wait of years with no guarantee of resettlement for people often with dependents at risk in their home country. It involves living in squalid conditions, great difficulty in working, discrimination, fear of harrassment by police and fear particularly for women, and a life with no opportunity to develop their gifts and contribute to society.
Many asylum seekers thought that for someone with courage, to take put one's life at some risk by fleeing to the possibility of a better life, and in the process entrusting one's life to a people smuggler, was both a reasonable and ethical option. I would not disagree with them.
Andy Hamilton | 25 February 2011
How easily we can demonize refugees and their methods of arrival and hold them in detention centres(gaols?)How slow ,expensive, cruel and wasteful is the administration for their entry to our country!Does anyone know how many Irish migrants have come to this country in the last two years(70,000?)How quickly they have been processed.
Thank you Andrew for your pertinent article and the conversation it has generated.
Chris | 25 February 2011
Considering a large portion of the present-day Australian population is descended from Irish emigrants fleeing economic and political persecution at home, it seems fairly hypocritical to take such a stance now against present day asylum seekers -a case of pulling up the ladder after reaching safety yourself! Or is it that the colour of most present day asylum seekers by boat is wrong??
Dr Michael Kissane | 26 February 2011
I am almost reluctant to enter this discussion, given that Andrew has already replied. I usually feel that the return of the original writer, commenting in response, should mark the close of the discussion.
But Andrew, I must ask why is the fear felt by refugees waiting in Indonesia "particularly [felt by] women"?
Because you give no reason for this assertion in your response, readers who know little about Indonesia can, and are likely to, infer that a refugee woman will be at greater risk of physical attack as a woman, in Indonesia than in Australia or in her country of origin. But this would not be true.
Belief in the sanctity of the human body and respect for women continues in Indonesia to a greater degree than in Australia. Despite Westernisation of major urban areas, the traditional respect for women has not been significantly degraded by commercialisation (as in "Sex sells") which we observe in major Australian cities.
I fully agree with the rest of your response, as also your original article. This unexplained assertion is something of a poison dart - so out of place in your otherwise well-argued humane comments.
Ian Fraser | 26 February 2011
Thanks Andy, for this great and very timely article. You are absolutely right in your views. Maybe you can get your work published in the Herald Sun and similar publications??
Congratulations on your work. It makes working with asylum seekers worthwhile, and is of course, a reminder of why we do it..
Katherine Rechtman | 26 February 2011
Thank you, Ian, for your comment and invitation to clarify what I meant. I can see that my sentence might bear the construction you gave it. I did not intend it, and I would wholeheartedly agree with your eloquent rebuttal of it.
What I meant was more generally intended. Asylum seekers anywhere are vulnerable to mistreatment and discrimination, and that too often takes the form of sexual harrassment and worse. That is not specific to particular nations. So male asylum seekers are often afraid for their wives and daughters both in the place where they are and in their own country from which they fled. That adds to their desire to find a place where they can find security and bring their threatened familes.
Great words, well thought out. Thanks, Andy.
Jim McDermott, SJ | 27 February 2011
Under international law it is not people smuggling to give refugees a ride and our parliament are well aware of that fact having been told by our courts that the Indonesian fishermen are not smuggling, having ratified the smuggling protocol which excludes anyone seeking asylum and anyone who helps them from any form of punishment.
Here we are the only nation in the world who have put the refugee convention into domestic law and now criminalise one form of transport in direct conflict with Article 31 of the convention which also forbids punishent due to method of arrival.
Most refugees I know have paid 5 or more different people for transport but we only jail the poor devils who would otherwise starve in Indonesia because we have stolen their fishing grounds and polluted them.
It is no more people smuggling than flying to the moon but they are an easier way to demonise the passengers.
No-one is running around Afghanistan enticing anyone to leave, if so they would pay them to leave instead of being paid.
Marilyn Shepherd | 27 February 2011
Thanks Andrew for your reply to my concern about the unguarded comment re refugees waiting in Indonesia.
And thank you, Marilyn Shepherd, for the detail re Article 31. It amazes me how so many Australians - perhaps a majority, given the support they have from parliamentarians on both sides of the House - continue to refer to asylum seekers as illegal immigrants.
And as for our courts, jailing the Indonesian fishermen and burning their boats is nothing short of revenge against those who are paid the least for their part in the refugees' flight.
Why revenge? Well, it's certainly not a deterrent! Punishing the fishermen is striking out in frustration at the ferrymen, because we cannot catch the organisers.
And the myth of Australia as the land of the fair go continues ...
Thank you Andrew for explaining in reasoned and compassionate terms why people become refugees. Of course, the reason that Tony Abbott, Scott Morrison,Julia Gillard, Kevin Rudd and others have vilified asylum seekers is because they are playing to the racist grandstand for their own political purposes. They never acknowledge that many refugees are in dire straits because of the US wars that they have supported. At the same time, it must be acknowledged that many people smugglers are opportunists who are prepared to risk other people's lives to make a profit. They are not alone in this regard, however. Many executives in big business do this everyday! It is a pity that Tony Abbott did not develop a sense of compassion and social justice when he was a student of the Jesuits at Riverview College in the early 1970s. Sadly, in those days, many there were not very progressive as those publishing Eureka Street today. Please continue your support for human rights for all.
Andrew (Andy) Alcock | 27 February 2011
This small story may have some relevance when looking at the storm over "people smugglers". In 1947 my late husband, than aged 22, engaged a "smuggler" to help him over a minefield to escape the repression of Russian communism in his birth country of Hungary. He also paid a "helper" to find him a place in a barrel in a truck to get him over the border into Austria where he (and others) were engaged as farm laborers until they got themselves into Italy and the luckydip of getting on a boat to Australia. He did not see his family again until the mid 80's when it became possible to travel there. He then worked for the government for 2 years before eventually gaining Australian citizenship. He was never a burden on this country which he loved.
Mary Maraz | 01 March 2011
Excellent thought provoking article. How can it be made more broadly accessible to the rest of the community and politicians??
Sue Foster | 08 March 2011
I have met "people smugglers" in their home land of Indonesia. They were like the asylum seekers , namely they were prepared to do whatever it took to earn enough to give their family a chance in this dog-eat-dog world called the non-western world. Most were fishermen. There were those who organised it and they are everywhere as the scum who parasitise off others and profit hugely. That of course is not the question. The question remains how will I treat the stranger who knocks on my door asking for help? The answer has little to do with who they are or why they came. The answer reflects the person that I am or want to be. I want to be someone who shows compassion and hospitality to the stranger.That is my Christ given mandate.
graham patison | 21 March 2011
One of the things we need to consider is the rumour among their own people that most of these Afghan and Pakistani asylum seekers are funded by Taliban. Vietnamese refugees were seen as 'poor' but only the rich could afford the price charged by people smugglers. The People smugglers may be part of some international crime syndicates, just like most of the Somali pirates who hijack ships.
walson | 24 March 2011
Margaret Dooley Young Writers Fellowship
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