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Translation from Ukrainian
Ukrainian belongs to the Slavic group, East Slavic subgroup of the languages. It closely relates to Belorussian and Russian. In most cases the speakers of these languages can understand each other without a dictionary.
The first theory concerning the origin of the Ukrainian language, is by the great Russian scientist Lomonosov, supposes that both Russian and Ukrainian come from one common Proto-Slavic language and the difference between them is explained by the fact that the Ukrainian language was influenced by Polish and Turkic and Russian was influenced by Finno-Ugric languages. But this theory was criticized because some of the most important and prominent differences between Russian and Ukrainian can't be explained by Polish or Finno-Ugric influences.
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The theory which appeared later also supposes the existence of a common language for Ukrainian, Russian and Belorussian, but the differences between the languages are seen as a result of several factors, not only the Polonization of Ukraine. A different theory appeared in modern Ukraine, struggling for its culture independence and originality. This theory says that no common Proto-Slavic language ever existed and the Ukrainian language is the result of the convergence of several old Ukrainian dialects. So, the idea is that the Ukrainian language appeared and developed independently from Russian. This theory, however, is not supported by the linguists outside Ukraine.
Some linguists believe that Russian, Ukrainian and Belorussian are the dialects of the same language, because they are mutually intelligible by the speakers, but most linguists consider them to be separate languages with the common origin.
Ukrainian is the official state language in Ukraine and its status gets a significant governmental support. The Ukrainian is the only language which can be officially used by the Ukrainian educational system and the state media. The Ukrainian language obtained this degree of importance only after the collapse of the Soviet Union and the changes have been very sharp and quick, as in the Soviet times, the Russian language had the dominant position. Nowadays it is still in intensive use, but the government forces people to use Ukrainian.
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- Research article
- Open Access
Evolution of hedgehog and hedgehog-related genes, their origin from Hog proteins in ancestral eukaryotes and discovery of a novel Hint motif
- Thomas R Bürglin1Email author
© Bürglin; licensee BioMed Central Ltd. 2008
- Received: 16 March 2007
- Accepted: 11 March 2008
- Published: 11 March 2008
The Hedgehog (Hh) signaling pathway plays important roles in human and animal development as well as in carcinogenesis. Hh molecules have been found in both protostomes and deuterostomes, but curiously the nematode Caenorhabditis elegans lacks a bona-fide Hh. Instead a series of Hh-related proteins are found, which share the Hint/Hog domain with Hh, but have distinct N-termini.
We performed extensive genome searches of the cnidarian Nematostella vectensis and several nematodes to gain further insights into Hh evolution. We found six genes in N. vectensis with a relationship to Hh: two Hh genes, one gene with a Hh N-terminal domain fused to a Willebrand factor type A domain (VWA), and three genes containing Hint/Hog domains with distinct novel N-termini. In the nematode Brugia malayi we find the same types of hh-related genes as in C. elegans. In the more distantly related Enoplea nematodes Xiphinema and Trichinella spiralis we find a bona-fide Hh. In addition, T. spiralis also has a quahog gene like C. elegans, and there are several additional hh-related genes, some of which have secreted N-terminal domains of only 15 to 25 residues. Examination of other Hh pathway components revealed that T. spiralis - like C. elegans - lacks some of these components. Extending our search to all eukaryotes, we recovered genes containing a Hog domain similar to Hh from many different groups of protists. In addition, we identified a novel Hint gene family present in many eukaryote groups that encodes a VWA domain fused to a distinct Hint domain we call Vint. Further members of a poorly characterized Hint family were also retrieved from bacteria.
In Cnidaria and nematodes the evolution of hh genes occurred in parallel to the evolution of other genes that contain a Hog domain but have different N-termini. The fact that Hog genes comprising a secreted N-terminus and a Hog domain are also found in many protists suggests that this gene family must have arisen in very early eukaryotic evolution, and eventually gave rise to hh and hh-related genes in animals. The results indicate a hitherto unsuspected ability of Hog domain encoding genes to evolve new N-termini. In one instance in Cnidaria, the Hh N-terminal signaling domain is associated with a VWA domain and lacks a Hog domain, suggesting a modular mode of evolution also for the N-terminal domain. The Hog domain proteins, the inteins and VWA-Vint proteins represent three different families of Hint domain proteins that evolved in parallel in eukaryotes.
- Conserve Cysteine Residue
- Naegleria Gruberi
- Cnidarian Nematostella Vectensis
- Early Metazoan Evolution
- Hint Domain
The Hedgehog (Hh) signaling pathway has been shown to be of fundamental importance for patterning and cell proliferation in animal development (for review see [1–4]). Mutations in this pathway cause congenital defects and several types of cancer such as basal cell carcinoma and medulloblastoma [5–8]. A key molecule of the pathway is Hh, a secreted ligand that can act as morphogen. Drosophila melanogaster has a single hedgehog (hh) gene, while mammalian genomes contain three paralogous genes, Sonic Hh (Shh), Desert Hh (Dhh), and Indian Hh (Ihh) [9]. In zebrafish, five hh genes are present due to an extra round of genome duplication during evolution of ray-finned fish [10, 11]. The Hh protein is synthesized as a precursor composed of two domains, the N-terminal signaling domain and the C-terminal autoprocessing domain. A substantial part of the autoprocessing domain shares sequence similarity with self-splicing inteins and therefore this domain has been named Hint [12]. C-terminal to the Hint domain is a sterol recognition region (SRR). A crucial function of the autoprocessing domain is to add a cholesterol moiety to the N-terminal signaling domain, which is required for the proper function of the N-terminal ligand [13–16]. In the nematode Caenorhabditis elegans no bona-fide hh is present, i.e. there is no gene that encodes both the N-terminal signalling domain as well as the C-terminal Hint domain. Instead ten genes encoding the C-terminal autoprocessing domain are found that, however, have N-terminal regions very distinct from Hh. Furthermore, a large number of additional genes are found that encode only these new N-terminal domains and lack the C-terminal autoprocessing domain. Overall, these genes can be grouped into four families that have been named quahog (qua), warthog (wrt), groundhog (grd) and ground-like (grl) and are collectively referred to as hh-related genes [17–19]. At present it is not clear, whether the C-terminal domains of the C. elegans Hh-related proteins can add a cholesterol moiety to the N-terminus analogous to Hh, since there are sequence differences in the SRR equivalent region. Therefore, this region of the Hh-related proteins was named ARR (adduct recognition region) [20]; here we refer to the combined Hint/SRR or Hint/ARR region as Hog domain for simplicity, as others have done as well [21].
The N-terminal domains of the C. elegans hh-related genes were not found in vertebrates and flies using blast searches, giving rise to the notion that these genes were perhaps derived from hh in early nematode evolution [17, 18]. Recently, a Hog domain containing protein, Hoglet, was discovered in the choanoflagellate Monosiga ovata, but its N-terminal region is distinct from Hh and other Hh-related proteins, instead sharing sequence similarity with cellulose-binding domains (CBD) [22]. Choanoflagellates are unicellular protists most closely related to multicellular animals [23, 24] and therefore Hoglet might represent an ancestral precursor form of Hh. A Hh protein was also described from the cnidarian Nematostella vectensis [25, 26], indicating that Hh already existed before the rise of bilaterian animals. An EST with sequence similarity to Hh was also recovered from the sponge Oscarella carmela [27], indicating that the "Hedge" domain originated before the advent of Eumetazoa. In order to understand the origin and evolution of the C. elegans hh-related genes, we had already performed cursory searches of the genome of the parasitic nematode Brugia malayi and found that it also contains several hh-related genes [18, 17]. Here we performed comprehensive searches of the genomes of the cnidarian N. vectensis [28], the nematodes B. malayi and Trichinella spiralis as well as the NCBI protein, DNA and EST databases to find additional hh and hh-related genes that may shed light on the evolution of these genes. In these searches we found a previously described gene from the fungus Glomus mosseae that shares sequence similarity with Hh through the Hog domain [29], but has not been considered in recent evolutionary analyses [22]. Furthermore, we found a number of additional genes with similarity to the Hog domain in Alveolata, moss, red algae, and other protists, indicating that the origin of the Hog domain occurred already in lower eukaryotes. As stated above, the Hog domain shares sequence similarity to self-splicing inteins, which have been found in Archaea, Bacteria, as well as fungi, algae and a few protists [30–32]. Recently, two other types of Hint related domains have been described, primarily from bacteria, that have been named bacterial intein-like proteins (BIL) type A and B [21, 33]. Several conserved sequence motifs within the Hint domain have been described for inteins that have been named motif A, B, E and F [34–37]. Our searches revealed also ORFs in Tetrahymena, fungi and several other protist branches that have similarity to the Hint domain via motifs A and B, but cannot be classified as inteins, Hog, or BIL domains.
Retrieval and analysis of sequences
hh-related genes in B. malayi and other Chromadorea
Number of hh and hh-related genes found in different species.
Gene structure
1 + 1?
Hog only
Unknown hog
A few ESTs were retrieved from other Chromadorea nematodes: In Meloidogyne incognita we found a gene with similarity to wrt-6 (Figure 2, 3, 4, 5, 6), and one grl gene, Msp3, which is expressed in the esophagal gland cells [40] (Additional file 8). In Parastrongyloides trichosuri a gene with similarity to wrt genes was found (Additional file 7).
hh and hh-related genes in Enoplea nematodes: Xiphinema sp. and Trichinella spiralis
Apart from the similarities in the regions N-terminal to the Hog domain indicated above, the remaining N-terminal sequences show no obvious similarities between each other or to any other proteins. Only the threonine-rich stretch is reminiscent of the 200 residue long threonine stretch in the N-terminal region of the choanoflagellate Hoglet protein [22]. However, this may be a case of convergent evolution. No Wart, Ground, or Ground-like domains could be detected in the genome of T. spiralis or in EST database searches restricted to Enoplea.
Based on phylogenetic analyses of the Hog domains, XC Xhog1, Xhog2, Xhog3, and Ts Qua-1 form a clade with the Quahog proteins (Figure 5, 6, Additional files 5, 6, 7). While N-terminal sequences for XC Xhog1, 2 and 3 are lacking they could be bona-fide Quahog proteins. A second, distinct clade is formed by Ts Xhog1, Xhog2, and XC Shog1, Xhog4, Xhog5 and Thog, indicating that they are derived from a common ancestor (Figure 5, 6, Additional files 5, 6, 7). In three cases, Ts Xhog1, Xhog2 and XC Xhog5), a common upstream sequence (Enop) has been identified (Figure 10), which seems to be specific to Enoplea nematodes, suggesting that at least in the cases of XC Shog1 and Thog the N-terminal regions have diverged relatively recently.
Almost all nematode Hh-related proteins form a distinct clade, the only exception being the Hh proteins, and Ts Xhog3 and XC S2hog, which are both very divergent and do not fall into the Hh clade of genes either (Figure 5, 6, Additional files 5, 6, 7). Two features distinguish the Hog domains of the nematode Hh-related proteins from those of the Hh proteins (Figure 1, 2, 3, 4, Additional files 1, 2, 3). 1) The regions corresponding to motifs K and L have characteristic differences in their conserved residues in nematode Hh-related proteins. 2) Two conserved cysteine residues are found in the central region of the Hog domain. When these two residues are mapped onto the X-ray structure of the C-terminal autoprocessing domain of Drosophila Hh [12], it emerges that they lie adjacent to each other and therefore could form a disulfide bond. This feature might stabilize this type of Hog domain in an extracellular environment, and this extra stability might possibly provide some new functionality. It is however not unique to nematode Hog domains. Zebrafish ihha and ihhb and fugu dhh (fhh) also have this extra cysteine pair, which must represent convergent evolution. It is worth pointing out that Ts Hh lacks the two cysteine residues and has motifs K and L as expected from a bona-fide Hh molecule. However, the quite divergent Ts Xhog3 protein, which lacks a Hedge domain, also lacks the cysteine residues and has motifs K and L.
hh and hh-related genes in Cnidaria
Last but not least, Nv 200640 is predicted to be 3592 amino acids long and is highly unusual. It is similar to the Hh proteins through the N-terminal Hedge domain (blast expected probability: 1e-18 to Ciona Hh), but no Hog domain follows (Additional files 10, 13). The Hedge domain is encoded by two exons, and after an intron of 600 bp many additional exons continue the ORF of the JGI prediction, but nowhere in this genomic region resides a Hog domain. Analysis of the ORF using the SMART server revealed that these extra exons encode multiple motifs with significant sequence similarity to other proteins (Additional file 13). The first motif, encoded by exons 3 and 4, contains a von Willebrand factor (vWF) type A domain (VWA). For example, the VWA domain of chicken collagen, type XIV, alpha 1 (undulin) is retrieved with a blastp probability of 8e-28. After the VWA domain, 21 CA (Cadherin repeat) domains follow, they occur as repeats in extracellular regions and are thought to mediate cell-cell contact when bound to calcium. Further follow two Immunoglobulin C-2 Type domains, two EGF repeats, a transmembrane region, and finally an SH2 domain.
The phylogenetic analysis of the cnidarian Hog domains reveals that they cluster primarily with the Hh Hog domains (Figure 5, 6, Additional files 5, 6, 7), albeit mostly with insignificant bootstrap values. The Hog domain of Nv 241466 Hh has the best similarity to the Hh Hog domains, and clusters with the deuterostome Hh proteins. Nv 140260 and Nv 239508 are most similar to each other, suggesting a likely duplication event within the cnidarian lineage. Nv 120428 and Acm DY579185 may also be related to these two proteins via their Hog domain (Figure 5, 6, Additional files 5, 6, 7), but the bootstrap values are not significant. The Nv 95413 Hh protein is rather divergent, and the Hydra sequence Hm CO905822 is also very divergent and does not from a clade with any of the N. vectensis sequences. Therefore, it is not possible to determine, whether all the cnidarian Hog genes originated all from a single ancestral gene in the cnidarian lineage, or whether hh and other Hog genes were already present before the split of Cnidaria and Bilateria. The Hedge domains of the three N. vectensis ORFs are more divergent than the bilaterian Hedge domains (Figure 9, Additional file 10). The Hedge domain of Nv 241466 Hh is most similar to bilaterian Hh proteins, with a best blast probability of 2e-52 to a fish Hedge domain. Nv 95413 Hh is more divergent, with a best blast probability of 5e-36, and Nv 200640 is the most divergent Hedge domain, with a probability of 1e-18 to a Ciona Hh.
Hog genes in lower eukaryotes
In order to detect Hh sequences from lower eukaryotes, tblastn searches were performed using the organism restriction "eukaryotes NOT bilateria". This recovered a number of genomic and EST matches from lower animals, fungi, plants and protists (Figure 2, 3, 4, Additonal files 9, 14). One EST was recovered from the sponge Oscarella carmela, which was previously described [27]. Analysis of this sequence shows that, while it does have a Hedge domain, the downstream sequence does not contain the start of a Hog domain in any frame (Additional file 10). No sequence similarity to a VWA domain is detected in that fragment either. Nevertheless, it indicates that as in the case of Nv 200640, this gene may not contain a Hog domain.
A match was detected to the gene GmGIN1 from the fungus Glomus mosseae, which belongs to the Glomeromycota, a sister group of ascomycetes and basidiomycetes and had already been described as having similarity to Hh [29]. The Hog domain has a blast probability of 7e-18 to the best matching Hh Hog domain, which is much better than the blast probability of choanoflagellate Hoglet to the best matching Hh Hog domains (4e-10). Furthermore, good matches to motifs J and K, as well as a region with similarity to motif L. Therefore, GmGIN1 contains a bona-fide Hog domain (Figure 2, 3, 4, Additional file 14). The upstream domain of GmGIN1 shares similarity with Ras-like GTPases, e.g. the Arabidopsis protein AIG1 (avrRpt2-induced gene 1) and the animal The IAN/IMAP subfamily [29]. However, this ORF lacks a signal peptide and may therefore not be secreted.
Overall, these results show that Hog domains occur in many different branches of the major groups of eukaryotes. However, multiple losses seem to have occurred, since in many branches we did not detect Hog domains, for example, in Arabidopsis thaliana and other higher plants, or in the currently sequenced ascomycetes and basidiomycetes, or in other sequenced organisms such as Dictyostelium.
Other genes of the Hh pathway in Enoplea and N. vectensis
Components of the Hh signaling pathway in N. vectensis and Xiphinema sp. The absence of a gene does not mean it is not present, it just may not have been sequenced yet. Numbers indicate the protein prediction in JGI (Nv) or the accession number (XC). For more information on pathway components and C. elegans genes see [18]. Best blast scores are given for the Nv predictions in parenthesis.
2), 88278 (e-100)
yes (2 copies)
ceh-14, ptd-2
247677 (4e-71)
1), 84424 (0.0)
ptc-1, ptc-3
2), 208236 (e-123), 92220 (4e-84)
79512 (e-135) #
136852 (4–63)
246114 (2e-89)
cubitus interruptus (Ci/Gli)
2), 116463 (3e-85)
In N. vectensis we found good orthologues for dispatched, dally-like, patched, smoothened, fused, sufu and Ci (Table 2). No obvious homolog was found for Ihog. In the case of Drosophila costa, good matches to its human homologs were found, and Drosophila costa is rather divergent. Recently it has been shown that the mammalian homologues of fused and costa do not play the same key role in the pathway as in flies, instead sufu plays a major role [42, 43]. Overall, it looks like most of the key players of the Hh pathway are present in N. vectensis so that it is clear that the pathway was already well established before the split of Cnidaria and Bilateria.
Genes with novel Hint-like (Vint) domains
The VWA-Hint proteins do not seem to have a signal peptide for secretion. The VWA domain is located at the N-terminus of the proteins, although in four cases a Ubox precedes the VWA domain (Figure 17, 18, 19). A region of around 300 residues separates the VWA domain from the Hint domain. This region has several small patches of conservation and one large region, that we propose to call Vwaint domain. At the C-terminus a Hint-like domain follows, which is of similar size as a Hog domain. However, the best conserved features are only motifs A and B, i.e. the N-terminal region of the Hint-like domain. One region shares a little similarity with motif F of inteins and BIL-Bs, but motifs J, K and L are lacking (Figure 17, 18, 19). The Hint-like domain is also rather different from inteins or Hog domains, the best blast matches of aTt 00471620 are to honeybee Hh with a probability 0.013. Therefore, these sequences cannot be classified as intein, Hog or Bil domains, and we refer to these genes as Vint genes. Vint genes are apparently so wide spread in eukaryotes that we have to assume that a common ancestor was present in early eukaryotes. However, Vint genes seem to be lacking in Arabidopsis, many fungi (for example, Saccharomyces cerevisiae), and in Metazoa. Multiple independent losses in different lineages seem the most likely explanation for this absence.
Our searches also revealed a group of proteins from bacteria that had a Hint-like domain at their C-terminus and shared some weak sequence similarity in their N-terminal region (Additional files 16, 17). At least some of these proteins are predicated to have signal peptides for secretion, and the upstream region has two cysteine residues conserved between all sequences. The Hint-like domains of these bacterial proteins are also quite divergent from inteins, Hog and BIL domains, and represent yet another subgroup. This subgroup has previously also been detected by Dassa and Pietrokovski [21]. The new members we retrieved here support the notion that this is yet another new type of Hint protein.
Hh and hh-related proteins in nematodes
In the more distantly related Enoplea nematodes Xiphinema sp. and T. spiralis a strikingly different pictures emerges. In both species we find both a hh gene as well as several hh-related genes. In T. spiralis we also find a quahog gene, and – based on the phylogenetic analyses – some of the Xiphinema genes could also be quahog genes. Two T. spiralis and one Xiphinema protein share a new motif (Enop motif) upstream of the Hog domain that appears to be specific to Enoplea nematodes. However, there are also a number of instances of N-terminal sequences that are very short. Several of these proteins cluster with the "Enop" proteins in the phylogenetic analyses, suggesting that they diverged from a common ancestor. However, two proteins with short N-terminal regions (Ts Xhog3 and XC Shog2) are rather divergent and do not reliably fall within the clade of nematode-specific Hog proteins ("Nema-Hog" proteins) in phylogenetic analyses. In particular Ts Xhog3 lacks the conserved cysteine pair usually found in Nema-Hog domains, and it shares motifs K and L with Hh Hog domains, indicating it could be derived from a Hh protein. Therefore, while these genes could have diverged from hh or Nema-Hog genes, it may also be possible that the represent ancestral genes that were lost in Chromadorea. In conclusion, we think that there were probably at least three different types of Hog genes in the common ancestor of Enoplea and Chromadorea, one hh gene, one quahog gene and one gene which give rise to the wrt/grd branch in Chromadorea and the Ts Xhog1/2 branch in Enoplea. But possibly up to five Hog genes could have existed in the common ancestor. The proliferation into further distinct groups such as wrt, ground and ground-like appears to have happened later in a branch specific manner.
Many different N-termini now exist in Nema-Hog proteins. Two possible mechanisms can explain this diversity: Either acquisition of new N-terminal domains, or divergent evolution of existing N-terminal domains. A relatively good case can be made that all Wart, Ground and Ground-like domains arose from a single common ancestor based on weak sequence similarities between the motifs [17]. This relationship is also supported by the phylogenetic analyses of the Hog domains. Therefore, multiple loss of the Hog domain must have occurred secondarily within the wrt and ground families. The presence of the rather short N-termini in Enoplea suggests that these regions have evolved and diverged through mutations, rather than by acquisition of a new domain. The threonine-rich stretch in XC Thog is very likely the result of polymerase slippage, though it is striking that this feature has evolved separately also in the choanoflagellate Hoglet protein [22]. It is also worth mentioning that some of the Caenorhabditis N-terminal domains have repetitive regions outside of the conserved Ground and Ground-like domains, mainly proline, glycine and serine. For example, Ce grl-23 has a 176 residue long stretch upstream of the Ground-like domain containing 125 glycine residues. In conclusion, most of the observed variability in the N-terminal domains of nematode Hh-related proteins is probably the result of sequence divergence from a progenitor, rather than acquisition of new domains. Loss of N-terminal domains in the case of C. elegans Hog-1, as well as loss of Hog domains did occur however.
A surprising observation is the fact that T. spiralis has a hh gene, but apparently lacks several components of the Hh pathway, such as Smoothened. Particularly noteworthy is that the components that appear to be missing are the same as in C. elegans. This would suggest that the signaling pathway was modified by loss already before the split of Enoplea and Chromadorea, even though hh was maintained in Enoplea. While one could imagine that Hh could be maintained in an animal parasite such as T. spiralis to affect host cells, this is very unlikely in the case of the plant nematode Xiphinema. It implies that Hh has an important function even in the absence of Smoothened, and it refutes the hypothesis that the Nema-Hog genes evolved directly from hh concomitantly with the other changes in the Hh pathway.
Hog proteins in Cnidaria
In Cnidaria we also encounter a complex situation with both Hh and Hh-related proteins. Both in N. vectensis and A. millepora we find bona-fide hh genes that have a Hedge and a Hog domain. Another gene is well conserved between N. vectensis and A. millepora and has a distinct, novel secreted N-terminal domain. Two further Hh-related proteins in N. vectensis have yet other, distinct N-termini. The upstream region of the two closely related genes retrieved from Hydra do not share any similarity with those in Nematostella, indicating divergent evolution. No sequence similarity of these new N-terminal motifs has been found outside Cnidaria.
The hh-related genes from Cnidaria are however distinct from those in nematodes, since the phylogenetic analyses of the Hog domains does not show them to be closely related. Therefore, we would like to suggest that – as in the case of the nematode hh-related genes – the Cnidarian N-terminal domains have evolved from common ancestors by divergent evolution rather than by domain acquisition.
The case of Nv 200640 is perhaps a special exception. In this protein we find an N-terminal Hedge domain fused to a large extracellular protein that contains a VWA domain as well as CA and EGF repeats, but it clearly lacks a Hog domain. The VWA domain is a 200 residue long domain first identified in von Willebrand Factor [44, 45]. VWA domains are found both in extracellular and intracellular proteins, such as non-fibrillar collagens, plasma proteins such as complement factors and integrins, and they mediate adhesion via metal ion-dependent adhesion sites. Likewise, the CA repeats also mediate adhesion in a Ca2+ dependent fashion. Therefore, the Nv 200640 protein is probably involved in cell adhesion. This shows that the Hedge domain can also evolve in a modular fashion and separate from the Hog domain. The EST recovered from sponges also has a Hedge domain that lacks the immediately following Hog domain, and may perhaps represent also a protein lacking a Hog domain.
Hog proteins in lower eukaryotes
We have recovered a substantial number of Hog domain proteins from many diverse groups of eukaryotes, mostly protists, such as red algae, moss, alveolates (ciliates, dinoflagellates, apicomplexans), cryptophytes, jakobids, haptophytes, cercozoa and Glomeromycota fungi. While some of these Hog sequences are quite divergent, they are invariably most closely related to Hog domain proteins from animals, and not to inteins, such as those found in fungi, or to BIL or Vint domains. Given the widespread occurrence in many of the major groups of eukaryotes ([46], we must conclude that Hog proteins were present already in the earliest eukaryotes. We find diverse N-termini associated with the Hog domain that are only conserved to limited extends within groups (case in point are the various conserved N-termini in nematodes). Many of these limited conserved N-termini have conserved cysteine residues, and in cases, where one can be quite confident of the start methionine, they start with a good signal peptide for secretion. Only in the case of the fungal protein GmGIN1 and the choanoflagellate Hoglet are distinct other N-terminal domains fused to the Hog domain. Therefore, we postulate that an ancestral Ur-Hog gene existed, with a secreted N-terminal domain and an autoprocessing Hog domain, that may have added a sterol or similar moiety to its secreted N-terminus. This gene evolved in concert with eukaryote evolution and was lost in several branches. In animals, the question arises about the origin of the Hedge domain. Both in sponge and in Nematostella we find a Hedge gene that lacks a Hog domain. Perhaps such a gene merged with a Hog domain in early metazoans. However, the reverse process is also possible: the Hedge domain evolved as an N-terminal variant of a Hog protein in early metazoans, and in the two Hedge genes in sponge and Nematostella the Hog domain was lost later. Both in Cnidaria and nematodes we find both hh and hh-related genes. Did the hh-related genes evolve twice independently from a hh precursor in each lineage? This is certainly the most parsimonious hypothesis. Nonetheless, in an alternative scenario, a hh and a hh-related gene could have been present in the common ancestor of eumetazoa, and the hh-related gene would have given rise to the cnidarian and nematode hh-related genes. For this hypothesis to be true, we would have to postulate three separate losses of hh-related genes: in deuterostomes, in lophotrochozoa, and in arthropods. While this seems rather unlikely, we do observe many losses of Hog genes in various branches of eukaryotes, as well as loss of the Hog domain only in a number of nematode genes so that such a series of losses may not be totally impossible.
Novel Hint genes
Our searches revealed new genes with Hint motifs merged to VWA domains. Given that a Hedge domain was found fused to a VWA domain in Nematostella we investigated this further and recovered a novel gene family. The well-conserved gene structure consists of a VWA followed by a new domain, termed Vwaint, followed by the "Vint"-type Hint domain. Unlike the Hog proteins, these proteins are most likely not secreted and instead are processed inside the cell. The Vint genes are present in many eukaryotic groups, but must have been lost multiple times, in particular in multicellular eukaryotes. Multiple loss seems to be a common theme also in Hog proteins and especially inteins [21, 32]. Inteins may be subject to special selective pressure for loss [21, 32], and this pressure may also extend to Hog and Vint proteins. However, gene loss is not uncommon. The N. vectensis genome contains a remarkable complexity of highly conserved gene families [25], and several instances of later gene loss in the protostome or deuterostome lineage, for example in the homeobox gene family, have been found [47, 48], indicating gene loss later in evolution is feasible.
We find that the evolution of Hh is more complex than anticipated, and that this gene family is not simply derived from an intein in early metazoan evolution. Both in Cnidaria and nematodes parallel evolution between hh and hh-related genes occurred. Given that the nematode-specific Hog domain (Nema-Hog) with its distinct features was already present in the progenitor of two very different nematode branches it may be possible that both Hh and some other Hog domain protein was already present in protostomes before the emergence of nematodes and was lost in other lineages such as arthropods. The finding of multiple Hog domain proteins in Cnidaria raises the possibility that multiple distinct types of Hog domain proteins also existed in ancestral Eumetazoa. Snell et al. (2006) suggested that a precursor of a Hedge domain fused to a Hog domain in early Metazoan evolution. However, our discovery that an Ur-Hog gene probably existed in the progenitor of eukaryotes makes if feasible that Hh evolved from an ancestral Hog gene without domain shuffling. In eukaryotes, we now know that at least three different types of Hint domains evolved in parallel: Hog, Vint, and inteins. At present we do not know the origin of the Hog and Vint domains, but perhaps new Hint domains from bacteria, such as described here and by Dassa and Pietrokovski [21] will shed light on that issue in the future.
Procedures for retrieving and analyzing sequences have been detailed in Hao et al. 2006 and Mukherjee and Bürglin 2007 [38, 48]. Briefly, B. malayi sequences were searched at TIGR [49]. Preliminary sequence data for B. malayi is deposited regularly into the GSS division of GenBank. This sequencing effort is part of the International Brugia Genome Sequencing Project and is supported by an award from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. ESTs, in particular nematode ESTs, were searched at NCBI [50]. The nematode ESTs are generated by the Washington University Parasitic Nematode EST sequencing project [51]. Many of the protist ESTs were generated by the Protist EST program [52]. The T. spiralis genome was searched using the GSC blast server at The Genome Sequencing Center of the Washington University School of Medicine [53]. N. vectensis sequences were searched at Stellabase [54, 28], and at the DOE Joint Genome Institute (JGI) [55]. Additional genome sequences such as for Naegleria gruberi, Physcomitrella patens and Monosiga brevicollis were searched at the JGI [55]. Zebrafish sequences were retrieved from ZFIN [56, 57]. The intein database was checked at New England Biolabs InBase [30, 58]. Manual sequence corrections were performed with the help of FGENESH and FGENESH+ at Softberry [59] and PPCMatrix [60]. ESTs representing the same locus were assembled using the CAP3 server at Iowa State University [61].
Species abbreviations. Fungi are prefixed with 'f', red algae with 'r', plants with 'p", Alveolata (ciliates, dinoflagellates, Apicomplexa) with 'a', jakobids with 'j', Cercozoa with 'c', Cryptophyta with 'cr', excavates with 'e', haptophytes with 'h', heterolobosea with 'l', and slime molds with 's'.
Species names
Acropora millepora (Cnidaria)
Anopheles gambiae (malaria mosquito)
Achaearanea tepidariorum (common house spider)
Branchiostoma floridae (Florida lancelet, Amphioxus)
Brugia malayi (nematode, Chromadorea)
Capitella sp. I ECS-2004 (polychaete)
Caenorhabditis briggsae (nematode, Chromadorea)
Caenorhabditis elegans (nematode, Chromadorea)
Caenorhabditis remanei (nematode, Chromadorea)
Drosophila melanogaster (fruitfly)
Drosophila hydei
Danio rerio (zebrafish)
Gryllus bimaculatus (two-spotted cricket)
Lytechinus variegatus (green sea urchin)
Hydra magnipapillata (Cnidaria)
Monosiga brevicollis (choanoflagellate)
Meloidogyne incognita (southern root-knot nematode, Chromadorea)
Mus musculus (mouse)
Monosiga ovata (choanoflagellate)
Nematostella vectensis (Cnidaria, starlet sea anemone)
Octopus bimaculoides (mollusc)
Oscarella carmela (sponge)
Parastrongyloides trichosuri (nematode, Chromadorea)
Patella vulgata (common limpet, mollusc)
Strongylocentrotus purpuratus (sea urchin)
Takifugu rubripes (fugu)
Trichinella spiralis (nematode, Enoplea)
Xiphinema index CSEQDL01 (nematode, Enoplea)
Amphidinium carterae (dinoflagellate, Alveolata)
Alexandrium tamarense (dinoflagellate, Alveolata)
Cryptosporidium muris (Apicomplexa, Alveolata)
Cryptosporidium parvum (Apicomplexa, Alveolata)
Karenia brevis (dinoflagellate, Alveolata)
Karlodinium micrum (dinoflagellate, Alveolata)
Tetrahymena thermophila (ciliate, Alveolata)
Bigelowiella natans (Cercozoa)
Guillardia theta (Cryptophyta)
Tritrichomonas foetus (Parabasalidea, excavates)
Ajellomyces capsulatus (ascomycetes, fungus)
Chaetomium globosum (ascomycetes, fungus)
Candida tropicalis (ascomycetes, fungus)
Glomus mosseae (Glomeromycota, fungus)
Gibberella zeae (ascomycetes, fungus)
Magnaporthe grisea (ascomycetes, rice blast fungus)
Neurospora crassa (ascomycetes, fungus)
Pleurochrysis haptonemofera (haptophytes)
Jakoba libera (jakobids)
Naegleria gruberi (heterolobosea)
Arabidopsis thaliana (plants)
Oryza sativa (rice, plants)
Physcomitrella patens (moss, plants)
Selaginella lepidophylla (club moss, plants)
Selaginella moellendorffii (club moss, plants)
Chondrus crispus (carragheen, red algae)
Gracilaria changii (red algae)
Griffithsia japonica (red algae)
Porphyra haitanensis (red algae)
Porphyra yezoensis (red algae)
Physarum polycephalum (slime mold, amoebozoa)
I would like to thank Shmuel Pietrokovski for helpful discussions and for sharing information. Preliminary sequence data for B. malayi is deposited regularly into the GSS division of GenBank. The Sequencing effort is part of the International Brugia Genome Sequencing Project and is supported by an award from the National Institute of Allergy and Infectious Diseases, National Institutes of Health. The Nematostella sequence data as well as other genome data such as Naegleria gruberi, Physcomitrella patens, and Monosiga brevicollis were produced by the US Department of Energy Joint Genome Institute [55]. The Trichinella data were produced by the Genome Sequencing Center at Washington University School of Medicine in St. Louis and can be obtained from their Web site [41]. This research was supported by grants from the Swedish Foundation for Strategic Research (SSF) and the Karolinska Institutet.
Authors' Affiliations
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This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

subset: commoncrawl


text:
Questions and Answers
"MobiLinc is unable to connect via a direct IP over HTTPS (externally) to my ISY."
"Does MobiLinc support multiple controllers?"
"What's the difference between Orchestrated MobiLinc and MobiLinc HD?"
"What does MobiLinc HD do on the iPhone?"
"Can I install my one paid app on multiple mobile devices?"
"How do I reinstall MobiLinc to my mobile device?"
"How do I get back a hidden device in MobiLinc?"
"Will MobiLinc support my IP Camera?"
"How do I connect to my IP Camera outside of my network?"
"How do I remove the red banner at the top of the screen when voice control is on and MobiLinc is running in the background?"
"How do I setup Push Notifications?"
"How do I upgrade MobiLinc Pro to MobiLinc HD or Orchestrated MobiLinc for iOS?"
"I'm having trouble with Alexa and MobiLinc Connect."
"I'm getting an error message that says MobiLinc can't reach my ISY through MobiLinc Connect or there's a pop-up message saying that my ISY is disconnected, what should I do?"
"Is the MobiLinc Connect cloud service required for my ISY?"
"How do I subscribe to MobiLinc Connect?"
"How do I add a second ISY to my MobiLinc Connect account?"
"My Push Notifications stopped working, what can I do to troubleshoot?"
"I have some question about geo-fencing. Where can I get more information?"
"Does MobiLinc support Wi-Fi based thermostats like the NEST?"
"I'm using Android 5.x and MobiLinc is unable to connect via a direct IP over HTTPS (externally) to my ISY."
"I have questions about the Extended Screens plug-in (Apple Watch/Today View)."


text:
This re-covered iPod is almost like hugging a tree, except it fits in the palm of your hand. So perhaps it's more like giving a tree a handshake and hearing your favorite tunes at the same time. Josh D, from Australia, took his Apple iPod Mini apart and built a brand new case from red cedar to update the otherwise outdated gadget into a stylish, natural, and woodsy example of heirloom design.
Rather than just recycling his old trusty iPod Mini when Josh got a new one, he decided to take care of a little mini project he had been meaning to do for some time. He took apart the Mini, removed the original cover and designed a new hardwood case using the original guts of the iPod. With the use of his trusty Dremel tool, he retooled a hardwood cover out of Australian Red Cedar and a clickwheel out of Camphor Laurel. Josh used brass plates for the bottom and top as well as brass screws to keep it all together.
The crafting of the clickwheel seems to be the most impressive aspect of the project. Josh shaved down the circular wooden piece to just a few millimeters thick and used double sided tape to adhere it to the iPod electronics. In his words, "the wooden clickwheel ended up being just as responsive as the original plastic clickwheel. I ended up shaving the clickwheel to only a couple millimetres thick, and the ipod's sensor picks up the signal no worries." There's even wooden accessories to go along with it – Josh re-coverd the iTrip module in Light Red Cedar as well as the iPod mini dock in Camphor Laurel.
The result is a beautifully finished piece that is likely to long outlast its cheap plastic counterparts, and would go perfectly with a set of slick wood speakers. We hope John will continue to update the casing with the latest guts, and compost it once it has lived through its useful lifecycle.
Via Designboom


text:
In a behind-the-scenes video, producer Eddie Kramer talks about "Mannish Boy", the new Jimi Hendrix song featured on the forthcoming From Both Sides of the Sky album.
Watch and hear it below.
Both Sides of the Sky is due out March 9. It features 13 studio recordings, 10 of which have never before been released.


text:
The secret of TCF's success is simple: As seasoned grievers reach
out to the newly bereaved, energy that has been directed inward
begins to flow outward and both are helped to heal. The vision
of The Compassionate Friends is that everyone who needs us will
find us and everyone who finds us will be helped.
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text:
Volkswagen e-up! concept – Click above for high-res image gallery
Way back in March of 2009, we first heard from a source who wished to remain anonymous that Tesla Motors co-founder Martin Eberhard might be back in the electric vehicle game. What we had been told was that Eberhard was doing some work with Volkswagen on electric vehicle projects. At the time, we contacted Eberhard, who told us that he wasn't ready to talk publicly about any new projects yet. Since we couldn't get any other confirmation, we let the story rest.
Green Tech Media is now reporting much the same thing we heard last year. Since that time, of course, Eberhard's defamation/breach of contract suit against Tesla has come and gone and in the last several months the Volkswagen group has unveiled three very different electric vehicle concepts. VW showed the E-up! city car in Frankfurt and Audi has shown two very different E-tron sports cars in Frankfurt and Detroit. VW has a research and development facility in Palo Alto, CA, not far from where Eberhard lives.
We've asked Eberhard for a comment on the situation and he has confirmed that he is indeed doing work with Volkswagen. Eberhard declined to provide any other details at this time other than to say, " my interests have not changed a lot." We certainly aren't surprised to see him involved because of his passion for electric vehicles. The U.S. is also a primary market for electrics being because of California mandates.
[Source: Green Tech Media]


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With a 3' length of 1/4" flat bar G clamped to the rear sprocket and a short length of the same bar clamped to the gearbox sprocket, i firstcheckd that the two were running parallel then measured the offset.... 3/8"
I turned down a piece of steel tube to the same inner and outer diameter as the standard sprocket distance piece but 1/4" narrower then turned the sprocket round and fitted it with the 1/8" dish in the way..... Jobsagoodun!!!!
- Posted using BlogPress from my iPhone


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Making Sense of Proposed Standards for Food Marketing to Children
Making Sense of Proposed Standards for Food Marketing to Children
A webinar on IWG standards
ChangeLab Solutions' National Policy and Legal Analysis Network to Prevent Childhood Obesity (NPLAN) and the Food Marketing Workgroup hosted a webinar to provide an insider's view of the recently released Interagency Working Group (IWG) standards for foods marketed to children.
Food and beverage companies spend approximately $2 billion per year marketing mainly fatty, salty, and sugar-laden products to children. Not surprisingly, this marketing affects children's diets and health. A childhood pattern of consuming nutrient-poor, calorie-laden food and drinks leads to an increased risk of heart disease, cancer, and diabetes.
With the goal of promoting children's health, Congress directed the IWG—comprised of the Centers for Disease Control and Prevention, Federal Trade Commission, Food and Drug Administration, and U.S. Department of Agriculture—to provide industry with recommended standards for food marketing to children under 17.
Webinar Presentation & Recording
Webinar Speakers:
- Samantha Graff, JD, NPLAN
- Margo Wootan, DSc, Center for Science in the Public Interest
- Bill Dietz, MD, CDC
- Michelle Rusk, JD, FTC
- Lori Dorfman, PhD, Berkeley Media Studies Group
Download the presentation as a PDF.
Webinar Resources
Get involved: contact the Food Marketing Workgroup at firstname.lastname@example.com
Interagency Working Group Proposed Voluntary Principles for Marketing Food to Children
Interagency Working Group Proposal on Food Marketing to Children Factsheet
Model Policies, Fact Sheets, and Other Resources
Model District Policy Restricting Food and Beverage Advertising on School Grounds
Creating Healthier Toy Giveaway Meals
State Attorneys General: Allies in Obesity Prevention
Identifying and Reporting Unfair, Misleading, and Deceptive Ads and Marketing
Select Studies
Food and Beverage Marketing to Children and Adolescents: An Environment at Odds with Good Health – Healthy Eating Research
Fast Food F.A.C.T.S. (Food Advertising to Children and Teens Score) – Yale University Rudd Center for Food Policy & Obesity
Cereal F.A.C.T.S. (Food Advertising to Children and Teens Score) – Yale University Rudd Center for Food Policy & Obesity
Food Marketing to Children and Youth: Threat or Opportunity – Institute of Medicine
Marketing Food To Children and Adolescents: A Review of Industry Expenditures, Activities, and Self-Regulation: A Federal Trade Commission Report To Congress – Federal Trade Commission
Nutritional Content of Television Food Advertisements Seen by Children and Adolescents in the United States – Bridging the Gap
Study Shows Uneven Progress on Youth Exposure to Food Advertising – Bridging the Gap
Predicting Support for Restricting Food Marketing to Youth – RWJF funded Health Affairs issue
Harnessing the Power of Supermarkets to Help Reverse Childhood Obesity – RWJF/Food Trust
Trends in the Nutritional Content of TV Food Advertisements Seen by Children in the US – Bridging the Gap
Target Marketing Soda & Fast Food: Problems with Business as Usual – Berkeley Media Studies Group for CCHE
The Soda and Fast-Food Industries Target their Marketing Towards Mothers of Color – Berkeley Media Studies Group for CCHE
Food and Beverage Marketing in the Digital Age Research Briefs - NPLAN, Berkeley Media Studies Group, Center for Digital Democracy
The Impact of Industry Self-Regulation on the Nutritional Quality of Foods Advertised on Television to Children - Children Now
Better-For-Who? Revisiting Company Promises on Food Marketing to Children - CSPI


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Sometimes guys forget themselves and say things they should never say to a woman, and then wonder why she got upset or looks at him with piercing eyes burning with disgust. Or the attraction she had for you just dies.
And to avoid damages, sometimes it's better to keep your mouth closed and let someone else take the heat. While you gets the love.
Almost all women are sensitive about how she looks, so don't mention anything that will negatively impact her self-esteem with regards to her appearance. Unless, of course, you're helping her put together an ensemble.
So watch out making comments about her weight, age, or shoes unless it's a genuine compliment on your part.
Now if you want to attract her, here are some things to never say if you don't want to get repelled. Remember what attracts women to men? Use that as a guide on how to act in front of her and the things you should say to her.
That means being a real man who's in control and in charge of his life and circumstance. Someone who doesn't seek to impress. So don't say anything that mentions your new sports car or how much money you've got in the bank which can only be interpreted as bragging.
If you want to take her out, don't seek permission. Just ask her out outright and plan for it. Do it in a confident and self-assured way and tell her what you're gonna do together. Make it sound like fun and that she'll miss out big-time if she didn't come.
Don't rely on her to think of where and what you're going to do. Since you're the one who asked her out, it's only right that you have some plan. If you don't, check out some date ideas.
Continue to lead the way for her throughout the date while keeping calm and not asking for mommy if she wants to do this or that. And to really enjoy the date, and not face a bomb waiting to explode, avoid talking bad about people she knows.
That includes her friends and family, no matter how much you don't like them. That just showing her your insecurity and talking trash about someone is never a good thing, anyway.
And when you stepped on a land mine about to explode, don't tell her to relax. Don't say it. Just go along and agree to what she's saying and show you understand. And next time, remember the things to never say to a woman.


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My Stamp Club
Children's Craft Birthday Parties
My Tips & Tricks
My Tutorials
My Contact Details
Saturday, 11 March 2017
Casing the Sale-a-bration Catalogue
When I saw one the projects made in the Sale-a-bration catalogue, using the "Designer Tee" stamp set, I knew that I had to case the card. I liked the overall layout of the card, but wanted to change the colour scheme and add a bit more bling to jazz it up some more. I love these colours together and thoroughly enjoyed making this card.
Birthday Cards
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Clinical Notes Autosave Update
The Clinical Notes unit has received some upgrades. The most important being a draft copy that is created every time you make a new or edit an existing note. The draft is autosaved incrementally to Praktika's servers once you type and it is your safeguard against the loss of your typed data in case of power failures or network interruptions. The draft can be used for copy-pasting into a new or an existing note. The draft is a very good indicator of how much of your note is actually saved at a particular period of time. Drafts are based on responses from our servers and what you see in a draft is surely saved in Praktika and cannot be lost. Draft headers are highlighted in red to separate them from the standard notes. After the normal save of a note, the corresponding draft gets removed. It will stay and show if there were issues during the save operation. We will also soon add the functionality to delete unnecessary or used up drafts.
User Restrictions Update
The new User permissions functionality allows to set up user access restrictions based on the day of the week, time of the day and the IP address. The restrictions apply per location. It means that the same user may have different access rights at various locations within the same business entity.User Restrictions Update
The most commonly used Cash Receipts Report has received some boost by providing various grouping options. Now you can group the displayed data by patient, by note or keep it ungrouped (per transaction)
Health Fund Autocomplete
The Health Fund input box has the autocomplete functionality (similar to the suburbs). Currently it lists the most common Australian Private Health Insurers. Soon it will be localised for our overseas users as well. Health Fund Autocomplete
This is a critical new feature that aims at preventing accidental logouts when a user clicks a close button, tries to quit the browser window or presses the "back" button of the browser.
Insert Balance Button
You may have noticed this new green square button next to the amount input field in the Payment Popup Screen. This button is a shortcut to enter the current appointment balance in the input. The purpose is to speed up and facilitate the entry of the amount balances, that can be quite tricky and laborious sometimes, especially when the cents are involved.
Medicare Expiry Date
This new data field is available both in the Desktop and iPad versions.
More Custom Icons to Choose
We have added more images to choose from in the custom icon setup. They include a smiley and sad faces, as well as a few other easily distinguishable icons.
Configuring Internet Explorer to better work with Praktika


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Turn to the nation's most objective and informative daily environmental news resource to learn how the United States and key players around the world are responding to the environmental...
March 10 — States said they have the tools to meet the Environmental Protection Agency's Clean Power Plan targets even as they quibble over how the final rule should be structured.
Representatives from Colorado, Minnesota, New York and Washington said the EPA's proposed rule, which would set unique carbon dioxide emissions reduction targets for the power sector in each state, is sufficiently flexible and achievable during a March 10 Senate briefing organized by the Georgetown Climate Center.
"We don't want EPA to weaken it overall as they consider changes to it because we want it to be as aggressive as possible, and we think we can achieve it with some of the improvements EPA can make," David Thornton, assistant commissioner of the Minnesota Pollution Control Agency, said.
The briefing comes in advance of a March 11 Senate Environment and Public Works hearing on state perspectives on the Clean Power Plan (RIN 2060-AR33) featuring representatives from California, Indiana, New York, Wisconsin and Wyoming. Under the proposed rule, states would develop their own plans to comply with the required emissions rate reductions.
"States are already achieving significant reductions in carbon pollution," Vicki Arroyo, executive director of the Georgetown Climate Center, said. "They're achieving these reductions cost effectively with benefits to their economies while reducing energy costs, driving clean energy innovation and improving public health."
Though many states, including supporters of the proposal, have raised concerns with how the EPA determined their emissions reductions targets and the stringency of the proposed interim deadlines, Martha Rudolph, director of environmental programs at the Colorado Department of Public Health and Environment, said the agency has been very responsive to state concerns.
"This is a very complicated rule and with its outreach, we're convinced the EPA is taking all of the comments seriously," she said.
Sam Rickets, director of Washington Gov. Jay Inslee's Washington, D.C., office, called the EPA's Clean Power Plan "essential" to addressing climate change. Rickets said the state of Washington is already seeing the effects of climate change on wildfires and shellfish.
One concern states have raised is with the 2012 baseline the EPA used in its rule. That means states such as Minnesota and Washington, which have already taken steps to reduce their emissions, may not get credit for those early efforts, representatives said.
While Washington supports the Clean Power Plan, Rickets said the rule doesn't account for hydroelectric generation, which provides 75 percent of the state's electricity. That means Washington needs to achieve even greater reductions from a handful of fossil fuel-fired units.
Thornton said the EPA could address those emissions rate targets in its final rule to provide more equity between states.
"Some states that haven't done so much aren't being asked to do so much," he said.
The proposal includes interim emissions rate targets to be met between 2020 and 2029 and a final goal for each state that applies beginning in 2030. The EPA as part of the proposal identified "building blocks" that states can use to meet the required emissions reductions, including heat rate improvements at coal-fired power plants, expanding use of natural gas-fired generating capacity, and investing in new renewable energy generation or through energy efficiency programs.
Jared Snyder, assistant commissioner for air resources, climate change and energy at the New York State Department of Environmental Conservation, said states in the Regional Greenhouse Gas Initiative have already shown that using a broad array of programs can produce cost-effective emissions reductions.
The Regional Greenhouse Gas Initiative is a collection of nine Northeast and mid-Atlantic states that have pledged to reduce carbon dioxide emissions from power plants by 50 percent from 2005 levels by 2020 as part of a regional emissions trading program.
The New York economy has continued to grow despite the state's pledge to curb its carbon dioxide emissions, Snyder said. In fact, he said the EPA could pursue even greater emissions reductions as part of its Clean Power Plan.
"Our experience shows the building block approach of the best system of emission reductions makes a lot of sense," Snyder said.
Thornton said Minnesota is "very excited" about the opportunities to pursue renewable energy and energy efficiency programs to comply with the Clean Power Plan.
"We do well in those two areas," he said.
Minnesota requires that 25 percent of its electricity must come from renewable sources by 2025, but the state is already on track to exceed that target, and the Legislature is considering boosting the goal to 40 percent, Thornton said.
To contact the reporter on this story: Andrew Childers in Washington at firstname.lastname@example.com
To contact the editor responsible for this story: Larry Pearl at firstname.lastname@example.com
All Bloomberg BNA treatises are available on standing order, which ensures you will always receive the most current edition of the book or supplement of the title you have ordered from Bloomberg BNA's book division. As soon as a new supplement or edition is published (usually annually) for a title you've previously purchased and requested to be placed on standing order, we'll ship it to you to review for 30 days without any obligation. During this period, you can either (a) honor the invoice and receive a 5% discount (in addition to any other discounts you may qualify for) off the then-current price of the update, plus shipping and handling or (b) return the book(s), in which case, your invoice will be cancelled upon receipt of the book(s). Call us for a prepaid UPS label for your return. It's as simple and easy as that. Most importantly, standing orders mean you will never have to worry about the timeliness of the information you're relying on. And, you may discontinue standing orders at any time by contacting us at 1.800.960.1220 or by sending an email to email@example.com.
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text: Hello you guys! I'm sitting at Ariel's place and finally being able to update this blog. It has been six days of travelling so far and what can I say.. I couldn't have had it any better. It's quite obvious that two days in Berlin or Rome is not enough. I'm not sure if even a lifetime is. Anyway we have been to coolest places ever, seen the most amazing stuff ever, walked more than ever and had the best hosts ever. I'm starting to post a little by little because there is so much to show you guys. So lets start with the day we went to the airport in my previous hometown, Helsinki ;D


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I absolutely love book sales. I always get so excited when I see the tables set up laden with books and I can't wait to start digging through those boxes! It occurred to me this past week that there's another aspect of the book sale that I find interesting: there are no preconceived notions acting as a barrier between me and the books.
While I obviously love libraries I think it's an interesting thought that they may influence our choice in books. For example, in my current library they use book stickers to help readers filter through the books on the shelves. These stickers cover essentially every genre, from mystery to romance to fantasy. But I've often wondered if those stickers actually stop people from picking up a book and reading the description. If a reader assumes "I don't like fantasy" then they may skip over every book with a fantasy sticker, eliminating the chance of them discovering a book or author that they really enjoy. By trying to make the books more accessible, libraries may influence our decisions and eliminate the possibility of that chance read.
You also can't get away from these labels on the internet. When reading a book review blog or looking up a book on Goodreads, people (including me!) have invariably categorized the books for us, tagging or sorting the books so that we may better understand what the book is about. And don't get me wrong, I've written before about how much I love tags and how useful they can be when searching for new books. But I think it's hard to escape these labels, and I have definitely had that moment when I think a book sounds good and then I realize it's labelled "mystery" or "thriller" and I think, do I really want to read this book?
Labelling, tagging or sorting is incredibly helpful as we look through books and try to choose ones that we want. Yet as I was shopping the book sale, I couldn't help but enjoy the lack of them. There were several large tables just labeled "fiction." That was it. Other than that, I was free to dig through boxes and see what kind of reads piqued my interest. By going by just the cover and book description and not knowing what categories the book fell into, I felt like I was opening myself up to that chance read, and finding something that I truly enjoy. Sometimes it's good to eliminate all of the labels that exist, and just judge the book by what you have in front of you: the book itself.
Here's what I picked up from the book sale. I can't wait to read these!
People of the Book – Geraldine Brooks
In 1996, Hanna Heath, an Australian rare-book expert, is offered the job of a lifetime: analysis and conservation of the famed Sarajevo Haggadah, which has been rescued from Serb shelling during the Bosnian war. Priceless and beautiful, the book is one of the earliest Jewish volumes ever to be illuminated with images. When Hanna, a caustic loner with a passion for her work, discovers a series of tiny artifacts in its ancient binding – an insect wing fragment, wine stains, salt crystals, a white hair – she begins to unlock the book's mysteries. The reader is ushered into an exquisitely detailed and atmospheric past, tracing the book's journey from its salvation back to its creation.
Reconstructing Amelia – Kimberly McCreight
Litigation lawyer and harried single mother Kate Baron is shocked when her daughter's exclusive Brooklyn private school calls to tell her that Amelia—her intelligent, high-achieving fifteen-year-old—has been caught cheating. But when Kate arrives at Grace Hall, she's blindsided by far more devastating news: Amelia is dead. Despondent, she's jumped from the school's roof. At least that's what Grace Hall and the police tell Kate. It's what she believes, too, until she gets the anonymous text: Amelia didn't jump. Now, Kate is going to find the truth—no matter where it leads. Sifting through Amelia's e-mails, text messages, and Facebook posts, Kate reconstructs the pieces of her daughter's life and the people in it, uncovering why she was on Grace Hall's roof that day—and how she died.
The Year of the Flood – Margaret Atwood
In a world driven by shadowy, corrupt corporations and the uncontrolled development of new, gene-spliced life forms, a man-made pandemic occurs, obliterating human life. Two people find they have unexpectedly survived: Ren, a young dancer locked inside the high-end sex club Scales and Tails (the cleanest dirty girls in town), and Toby, solitary and determined, who has barricaded herself inside a luxurious spa, watching and waiting. The women have to decide on their next move–they can't stay hidden forever. But is anyone else out there?


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28" x 44" Moveable Curb Sign
28" x 44" Moveable Curb Sign These weather resistant outdoor curb signs have a snap frame and are double-sided. They can be used as pavement signs, sidewalk signs, driveway or entryway signs to deliver your message any time of the day. The heavy duty flex spring system allows the sign to withstand the heaviest gust of wind. Complete with built in wheels it can be moved easily simply just tilt and roll it anywhere.
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Contact David
+44 (0) 1263 733195
+ 44 (0) 1263 738270
About David
David has spent his entire career at Keys, having joined in 2001. During that time he has amassed a wide experience in several departments, and as well as his role as General Sales Manager, he conducts auctions for other departments, and is the firms Transport Manager.
Born and bred in Norfolk, David is married with two young children. He is a keen sportsman, running, swimming and playing football, rugby and squash.
Forthcoming General Sales
There are no forthcoming sales for this department


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Dell "charged me $45 to remove spyware"
THE FOUNDER of an IT training and consultancy company Field Expert, here, is mightily miffed that Dell charged him $45 to remove what he believes is 'spyware' pre-installed on his nice shiny new computer.
Michael Amor Righi said that he knew that when the Dell machine arrived it would be full of software that he would never use such as AOL coach, Dell Picture Studio and Internet Explorer. But writing in his bog here, he says he was shocked to discover My Way Search Assistant. Dell 'charged me $45 to remove spyware'
Back to: PC Security, privacy news


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2017: "Reaching New Heights" in Calgary, Canada, October 11-14, 2017
2016: "Telling the Story of Teaching and Learning" in Los Angeles, California, USA, October 12-15, 2016
2015: "Leading Learning and the Scholarship of Change" in Melbourne, Australia (Oct 27-30)
2014: "Nurturing Passion and Creativity in Teaching and Learning" in Quebec City, Quebec, Canada (Oct 22-25)
2013: "Critical Transitions in Teaching and Learning" in Raleigh, North Carolina, USA (Oct 2-5)
2012: "Research on Teaching and Learning: Integrating Practices" in Hamilton, Canada (October 24-27)
2010: "Global Theories and Local Practices: Institutional, Disciplinary and Cultural Variations" in Liverpool, England, United Kingdom (October 19-22)
2009: "Solid Foundations, Emerging Knowledge, Shared Futures" in Bloomington, Indiana, United States (October 22-25)
2008: "Celebrating Connections: Learning, Teaching, Scholarship" in Edmonton, Alberta, Canada (October 16-19)
2007: "Locating Learning: Integrative Dimensions in the Scholarship of Teaching and Learning" in Sydney, Australia (July 2-5)
2006: "Making a Greater Difference: Connecting to Transformational Agendas" in Washington, DC, USA (November 9-12)
2005: "Commitment, Community, and Collaboration" in Vancouver, British Columbia, Canada (October 14-16)
2004: "The Scholarship of Teaching and Learning: Perspectives, Intersections, and Directions" in Bloomington, Indiana, USA (October 21-24)
ISSOTL is committed to offering conference venues in North America and around the world. We welcome proposals from appropriate sites for future conferences. For more information, please contact the current ISSOTL President.
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In a little Hungarian university town, at the turn of the century, there exists a small whorehouse. On an ordinary evening, the typical activities of the house include the girls and their madame taking a trip to the legitimate theater to see a play. Their dress and comportment outside the house are exemplary. Then they return and open for business, turning on the obligatory red light. A poor medical student is one of the house's beloved customers whose lack of cash is not an obstacle. One night during a...more
All Egy Erkölcsös Ejszaka cast + crew photos
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Fans of Summoning will want to pick up this debut from Norway's Eldamar almost immediately. Not only is it Tolkien inspired, but it is also atmospheric/ambient black metal by which a female vocalist (uncredited but used quite a bit, is it even a real woman?) performs a heavy degree of chanting/vocalizing amidst the hefty scowls of project mastermind Matthias Hemmingby. The production is especially misty, but feels quite cool due to the use of crystalline keyboard sections. It feels like there might be a real drum kit here, but I'm not real sure and technology is pretty awesome these days, so it's tough to tell. As you might expect, this is a very tough record to sort of walk you through as it doesn't really seem like it's about separate experiences at all. Rather I feel like this album is one large piece, in which several sections seem to comprise the whole.
There are however, a few lighter and atmospheric moments like "Travel In Woods" which reminds me a little of the fairy music from Link To The Past, as well as "Valkyrjur Ancient One" which reminds me of a climb up a frosty mountain. I can literally feel the chill of the wind on my back from listening to this (seriously, did it just get colder in here?) and feel that it captures the atmosphere perfectly. We also have "Galadwen The Eldar" which feels almost romantic in it's ethereal and majestic nature. That's just plain beautiful. Removing those though, we're left with a rather solid mix of raw black metal, female vocalizing (is she an effect?) and the same chilly keyboard pieces – which definitely work in the mix. It does really sound like Summoning if they came from Norway and I think they'd be flattered to see their style passed onto the next generation of musical performers. Once again, if you like Summoning and similar acts, you will definitely want to have a copy of The Force Of The Ancient Land in your collection.
(8 Tracks, 73:00)


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Famous OMs
Some famous Old Maidstonians
There is a list of more than 40 Wikipedia entries for Old Maidstonians at Famous Old Maidstonians. Some are described in a book written and published by LLC Press. Among them are the following.
Richard Beeching Physicist, engineer, Chair of British Rail
James Burke Journalist, historian and author
Andrew Dilnot Economist. Chair of the UK Statistics Authority, Warden of Nuffield College, Oxford and author of the Dilnot Report on care of the elderly.
Francis Fane, 1st Earl of Westmorland
David Flatman Rugby Player
Nick Gibb MP
Steven Howarth AKA Desmond Wolfe and Nigel McGuinness. Wrestler.
Philip Langridge Opera singer
General Sir Frederick Dobson Middleton
Philip Moore Organist and composer
John Pugh MP.
Frank Sando Athlete (OM President, 2007-8)
Christopher Smart Poet
Shaun Williamson Actor
The School has produced historical material which gives many more names: here's the link


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DIY professional development
The story goes that when money gets tight in higher education, professional development is often one of the first things cut for IT professionals. One would hope that no organization would cut their professional development budget completely, but there are probably some that do. In this sort of environment where we have shrinking budgets for training opportunities but a large population that has a penchant for learning, it becomes possible to get creative in offering professional development. A do-it-yourself model becomes an appealing way in which a community can come together to help each other, and you need three ingredients to make the process enjoyable for instructors and participants alike.
Ingredient 1: Expertise and willingness to share
The first ingredient you need to do cost-effective DIY training and development is a community that has expertise and a willingness to do the work to share that expertise with others. Training is a lot less risky than actual project work because of a lower time commitment. A project requires significant time to do the actual work and will often span a significant portion of the calendar. For a member of the community to facilitate or teach a session about something they know, they have to spend time preparing and time in the training, but that commitment is much more finite than technical project work.
There are many reasons to be a facilitator or instructor, but I would like to specifically mention a couple here. One is that teaching reinforces what you know, helps you know your material better. Two is that it makes you more valuable to the organization because you are no longer just sharing the fish you catch but also helping others catch their own fish. Every IT professional should consider these as important to their career growth.
Some people with expertise will likely need some encouragement and offers of help in order to step up to a facilitator or instructor role. As the low hanging fruit starting coming down, work needs to be done to identify and recruit additional facilitators and instructors. That's what the third ingredient can help do.
Ingredient 2: People willing to learn
It is irrelevant to have a teacher if you do not have students. This is where the legwork starts increasing. The "if you build it, they will come" concept only goes so far. Before the facilitator starts preparing material for the instruction, it is necessary to know whether you have a critical mass of participants that will be interested in attending the training. While the facilitator can be a good starting point by identifying people they think will be interested, it can significantly increase the work of the facilitator if it becomes their responsibility alone to find all the people interested in participating.
Network effects can play a significant role here with questions like, "Can you identify three people that you think would be interested in participating in this opportunity?" If you ask that of each person, you can quickly build a list of interested participants that can put you in a position to make a go/no go decision.
Ingredient 3: Help with logistics
In a higher education environment, we have a lot of resources "freely" available that are needed for instruction. We have things like classrooms and conference rooms for space, systems for marketing events and taking registrations, and computer labs for more technical sessions. Organizing all those resources is a pretty significant task though, and putting that work on facilitators makes being a facilitator unappealing to many.
Making someone responsible for doing the logistics of your DIY professional development will take a significant burden off the people you are calling upon to spend their time as facilitators and instructors. That someone can also add more to the equation than basic instructional space and registration logistical management though. They can also offer a broader coordination to the activities in terms of scheduling, recruiting facilitators and gathering interested participants. The coordination also makes a single point of contact that can go out for funding if any additional money is needed. It is possible to do DIY training without this higher level coordination, but the value of these opportunities goes up significantly with some coordination and planning.
If you look around your higher ed IT environment, you will probably see people already doing some of these things. With a little help and some coordination, you can turn an informal network of activities into a extremely valuable set of opportunities of which your institution can be proud.


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Self-deception affects everyone to some degree. Lives are lost and incredible amounts of time, money and resources are wasted each day because of it. Knowledge and disciplined vigilance are useful tools against it. So is hiring a professional.
In real estate the financial impact of self-deception can be enormous. The right real estate professional will employ his or her expertise and objectivity in your service to guide you away from making fundamental mistakes caused by self-deception.
Author and blogger Dan Ariely, the James B. Duke Professor of Behavioral Economics at Duke University, brings to light one sort of real estate self-deception in this recent blog post at Predictably Irrational.
A recent study conducted by Zillow finds what they call a "Not My House! Sentiment," where despite the evidence that 77% of U.S. homes actually declined in value in the past year, 62% of homeowners believe their own home's value has increased or stayed the same… – Dan Ariely
We've encountered home sellers who seemed to feel that their home was worth more simply because they lived in it. It's hard to beat that for self-deception!


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Meadowvale Village also has a conservation area in which you can do a whole lot such as BBQ, hiking, cycling and even bird watch, take photos or simply take your dog for a walk. This is located at 1255 Old Derry Rd, Mississauga from the West side entrance, and the East side entrance is 1081 Old Derry Road West, Mississauga.
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I have been volunteering with the Syrian Arab Red Crescent (SARC) Deir Ezzor branch since the end of 2007.
I have participated in many training courses including disaster management, risk reduction, first aid, community health care, and hygiene promotion.
We are all committed to our principles of humanity, impartiality and neutrality in helping the needy, which we have been doing since the beginning of the crisis in Syria.
I work as a first-aider. We face real risks and have even faced the death many times.
We have entered areas which were inaccessible for the others. Only SARC teams - water teams, distribution teams, first aiders - have been able to reach these areas and provide help. We have evacuated bodies as well from hard-to-reach areas.
We were able to reach people in need because everyone understands we abide by the seven fundamental Red Cross Red Crescent seven principles, especially neutrality and impartiality.
Since las year, I have been studying in the petrochemical engineering faculty. When I finish my studies, I will have my certificate, in addition to my experience working with my SARC family and friends.
I continue my volunteering work to give a hand for people in need and to protect dignity and humanity.
What I hope is that everybody respects our humanity, our emblem, and our volunteers. I am proud to wear this emblem on my chest.
The International Federation of Red Cross and Red Crescent Societies (IFRC) is the world's largest humanitarian organization, with 190 member National Societies . As part of the International Red Cross and Red Crescent Movement, our work is guided by seven fundamental principles; humanity, impartiality, neutrality, independence, voluntary service, unity and universality. About this site & copyright